diff --git a/notebooks/beta_catenin_dou/analysis_output/AMOT_statements.html b/notebooks/beta_catenin_dou/analysis_output/AMOT_statements.html new file mode 100644 index 000000000..700fad78c --- /dev/null +++ b/notebooks/beta_catenin_dou/analysis_output/AMOT_statements.html @@ -0,0 +1,1259 @@ + + + + + + + + + + + + Statements for AMOT + + + + + + + + + + + + + + + + + + + + + + + + + + +
+ + + + + + + +
+ + +
+
+
+

+ Statements +

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| + + + + + + geneways + + + + + + tees + + + + + + gnbr + + + + + + semrep + + + + + + isi + + + + + + trips + + + + + + rlimsp + + + + + + medscan + + + + + + eidos + + + + + + sparser + + + + + + reach + + + + + reading + + + +
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+ + + +
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+ + + + + + + + +
+
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+ + + +
+ + + + + + + + +
+ + + +
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+ + + + + +
+
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+ AMOT binds CTNNB1. + + 1 / 1 + + +
+
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+ + + + + + + + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
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+ + + +
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+ + + + + No evidence text available + + + +
+ + + +
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+
+ + + +
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+
+ + + +
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+
+
+ + + +
+
+
+
+
+ + + +
+
+ + + + \ No newline at end of file diff --git a/notebooks/beta_catenin_dou/analysis_output/APCDD1_statements.html b/notebooks/beta_catenin_dou/analysis_output/APCDD1_statements.html new file mode 100644 index 000000000..9c83de0a5 --- /dev/null +++ b/notebooks/beta_catenin_dou/analysis_output/APCDD1_statements.html @@ -0,0 +1,1517 @@ + + + + + + + + + + + + Statements for APCDD1 + + + + + + + + + + + + + + + + + + + + + + + + + + +
+ + + + + + + +
+ + +
+
+
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+ Statements +

+
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| + + + + + + geneways + + + + + + tees + + + + + + gnbr + + + + + + semrep + + + + + + isi + + + + + + trips + + + + + + rlimsp + + + + + + medscan + + + + + + eidos + + + + + + sparser + + + + + + reach + + + + + reading + + + +
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+ + + + + + + + +
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+
+ + + +
+ + + + + + + + +
+ + + +
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+ + + + + +
+
+
+ APCDD1 binds CTNNB1. + + 5 / 5 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + 1 + + + + + + + + + + + + 1 + + + + + + 3 + + + + + + +
+
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+
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+ + + +
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+ + +
+ sparser + +
+ +
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+ + + +
+ + + + + "Furthermore, APCDD1 expression was negatively associated with nuclear β-catenin expression and transcription factor/lymphoid enhancer binding factor 1 transcriptional activity in the present study." + + + +
+ + + +
+ + + + + + 29085490 + + + + +
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+
+ + + +
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+ + +
+ trips + +
+ +
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+ + + +
+ + + + + "Functional studies using ex vivo and in vitro OL systems revealed that Apcdd1 promotes OL differentiation, suppresses Wnt signaling, and associates with β-catenin." + + + +
+ + + +
+ + + + + + 25946682 + + + + +
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+
+ + + +
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+
+
+
+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "Functional studies using ex vivo and in vitro OL systems, revealed that Apcdd1 promotes OL differentiation, suppresses Wnt signaling, and associates with beta-catenin." + + + +
+ + + +
+ + + + + + 25946682 + + + + +
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+ + + +
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+ + +
+ reach + +
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+ + + +
+ + + + + "Consistent with its expression dynamics, functional studies revealed that it is sufficient to promote OL differentiation and suppresses beta-catenin dependent Wnt activation, which is mediated by an association between Apcdd1 and beta-catenin." + + + +
+ + + +
+ + + + + + 25946682 + + + + +
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+ + + +
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+ + +
+ reach + +
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+ + + +
+ + + + + "Importantly, that Apcdd1 suppresses beta-catenin dependent Wnt activation and associates with both beta-catenin and LRP6, suggests that it functions as a bridge between the proximal Wnt receptor complex and the distal nuclear effectors." + + + +
+ + + +
+ + + + + + 25946682 + + + + +
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+ + + +
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+ + + +
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+ + + + \ No newline at end of file diff --git a/notebooks/beta_catenin_dou/analysis_output/CALML3_statements.html b/notebooks/beta_catenin_dou/analysis_output/CALML3_statements.html new file mode 100644 index 000000000..836448ebf --- /dev/null +++ b/notebooks/beta_catenin_dou/analysis_output/CALML3_statements.html @@ -0,0 +1,1259 @@ + + + + + + + + + + + + Statements for CALML3 + + + + + + + + + + + + + + + + + + + + + + + + + + +
+ + + + + + + +
+ + +
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+ Statements +

+
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| + + + + + + geneways + + + + + + tees + + + + + + gnbr + + + + + + semrep + + + + + + isi + + + + + + trips + + + + + + rlimsp + + + + + + medscan + + + + + + eidos + + + + + + sparser + + + + + + reach + + + + + reading + + + +
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+ CTNNB1 activates CALML3. + + 1 / 1 + + +
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+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
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+ + + +
+ + + + + "This suggests that diminished Wnt and beta-catenin signaling can partially rescue the early lethality that is likely caused by excessive beta-catenin signaling, but it can not rescue the CLP phenotype that may be caused by both excessive beta-catenin and defective JNK signaling." + + + +
+ + + +
+ + + + + + 30760477 + + + + +
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+ + + +
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+ + + +
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+
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+ + + +
+
+
+
+
+ + + +
+
+ + + + \ No newline at end of file diff --git a/notebooks/beta_catenin_dou/analysis_output/CTNNA2_statements.html b/notebooks/beta_catenin_dou/analysis_output/CTNNA2_statements.html new file mode 100644 index 000000000..3df8f7a8d --- /dev/null +++ b/notebooks/beta_catenin_dou/analysis_output/CTNNA2_statements.html @@ -0,0 +1,1450 @@ + + + + + + + + + + + + Statements for CTNNA2 + + + + + + + + + + + + + + + + + + + + + + + + + + +
+ + + + + + + +
+ + +
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+
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+ Statements +

+
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| + + + + + + geneways + + + + + + tees + + + + + + gnbr + + + + + + semrep + + + + + + isi + + + + + + trips + + + + + + rlimsp + + + + + + medscan + + + + + + eidos + + + + + + sparser + + + + + + reach + + + + + reading + + + +
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+ + + +
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+ CTNNA2 binds CTNNB1. + + 4 / 4 + + +
+
+
+ + + + + + + + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 3 + + + + + + +
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+ + + +
+ + + + + "Both alphaE- and alphaN-catenin bind to beta-catenin with a Kd of 20 nM, and this affinity is increased by an order of magnitude when cadherin is bound to beta-catenin." + + + +
+ + + +
+ + + + + + 24692547 + + + + +
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+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 26344197 + + + + +
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+
+ + + +
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+ reach + +
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+ + + +
+ + + + + "Thus, this NH 2 -terminal domain is essential for alphaN-catenin binding to beta-catenin." + + + +
+ + + +
+ + + + + + 9362521 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "At adhesion sites, beta-catenin and alphaN-catenin form a complex that is linked via alphaN-catenin to the actin cytoskeleton, thus providing a potential link between cadherins at the cell surface and the actin cytoskeleton within the leading processes of radially migrating neurons." + + + +
+ + + +
+ + + + + + 27151949 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + +
+
+
+
+
+ + + +
+
+ + + + \ No newline at end of file diff --git a/notebooks/beta_catenin_dou/analysis_output/CTNNB1_statements.html b/notebooks/beta_catenin_dou/analysis_output/CTNNB1_statements.html new file mode 100644 index 000000000..8f1892912 --- /dev/null +++ b/notebooks/beta_catenin_dou/analysis_output/CTNNB1_statements.html @@ -0,0 +1,45090 @@ + + + + + + + + + + + + Statements for CTNNB1 + + + + + + + + + + + + + + + + + + + + + + + + + + +
+ + + + + + + +
+ + +
+
+
+

+ Statements +

+
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| + + + + + + geneways + + + + + + tees + + + + + + gnbr + + + + + + semrep + + + + + + isi + + + + + + trips + + + + + + rlimsp + + + + + + medscan + + + + + + eidos + + + + + + sparser + + + + + + reach + + + + + reading + + + +
+
+ + + +
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+ + + + + + + + +
+
+
CTNNB1 affects CTNNB1
+
+
+ + + + + + + + + + + + + + 18 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 4 + + + + + + 169 + + + + + + +
+
+
+
+
+ + + +
+ + + + + + + + +
+
+
CTNNB1 activates CTNNB1.
+
+
+ + + + + + + + + + + + + + 5 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 43 + + + + + + +
+
+
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 bound to ANRIL activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "In the present work, we confirm that ANRIL specifically binds to beta-catenin and increases the transcriptional activity of the WNT and beta-catenin pathway." + + + +
+ + + +
+ + + + + + 29463902 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to TFCP2 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The mechanism study revealed that TFCP2 interacted beta-catenin, enhanced the interaction between beta-catenin and TCF4, and activated beta-catenin and TCF signaling." + + + +
+ + + +
+ + + + + + 29050300 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to AXIN activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "When the Wnt pathway is not engaged, CK1 and GSK3beta phosphorylate Axin bound beta-catenin to drive beta-catenin to the proteasome for disruption." + + + +
+ + + +
+ + + + + + 29238040 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to USF1 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "OGT contributes to beta-catenin stabilization [XREF_BIBR, XREF_BIBR] and consequently to the regulation of miR-483-3p by the CTNNB1 and USF1 complex at the E-box element of the miR-483 promoter." + + + +
+ + + +
+ + + + + + 29867024 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to LEF1 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "MALDI-TOF mass spectrometry (MS) identified two CK2 phosphorylation sites (S42, S61) within the amino terminus of hLEF-1, and mutation of these sites reduced binding to beta-catenin in vitro and transactivation in vivo." + + + +
+ + + +
+ + + + + + 17113388 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to MUC1-C activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The functional significance of the MUC1-C and beta-catenin interaction is supported by the demonstration that MUC1-C stabilizes beta-catenin by blocking GSK3beta mediated phosphorylation of beta-catenin and thereby its proteosomal degradation." + + + +
+ + + +
+ + + + + + 28643330 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to GSK3 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Typically, beta-catenin is activated either as a result of GSK-3 inactivation (via its phosphorylation by AKT) or by the recruitment of axin, beta-catenin and GSK-3 to a ternary complex of Frizzled, phosphorylated Dishevelled and phosphorylated LRP5/6 at the plasma membrane (Wnt signaling) [XREF_BIBR, XREF_BIBR]." + + + +
+ + + +
+ + + + + + 28700668 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to EZH2 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "EZH2 may directly interact with beta-catenin inducing nuclear accumulation and activation of Wnt and beta-catenin signaling." + + + +
+ + + +
+ + + + + + 28881068 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to SPN activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "The intracellular domain of CD43 interacts with beta-catenin and causes an upregulation of the beta-catenin target genes c-MYC and CyclinD1." + + + +
+ + + +
+ + + + + + 15003504 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to SR proteins activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Biochemical experiments indicate that both SR proteins bind to beta-catenin mRNA and enhance beta-catenin synthesis." + + + +
+ + + +
+ + + + + + 23592547 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to factor activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Finally, beta-catenin interacts with T-cell factor and lymphoid enhancer binding factor (TCF/LEF) transcription factors and activates Wnt and beta-catenin target genes such as c-MYC and Cyclin D1 [28-31]." + + + +
+ + + +
+ + + + + + 23927962 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to SALL4A activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Furthermore, both SALL4A and SALL4B isoforms can bind beta-catenin protein and synergistically activate the Wnt and beta-catenin signaling pathway 65." + + + +
+ + + +
+ + + + + + 26892498 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to SOX1 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "SOX1 interacts with beta-catenin and induces a proteasome independent down-regulation of beta-catenin." + + + +
+ + + +
+ + + + + + 25427424 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Ubiquitinated CTNNB1 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "By inducing the ubiquitination of β-catenin, NEDD4L could repress the activation of the Wnt/β-catenin signaling pathway, and restrict the CTHRC1/HIF-1α axis due to the CTHRC1 expression-promoting effect of β-catenin; then, CTHRC1 and HIF-1α suppression could attenuate the viability and differentiation of LFs, thereby impeding the formation and progression of IPF." + + + +
+ + + +
+ + + + + + 34512149 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to TCF/LEF activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Beta-catenin then translocates to the nucleus and interacts with TCF/LEF which stimulates the beta-catenin downstream target genes (PDK, MTC-1, cMyc, cyclin D1, Cox 2, AXIN 2, etc.) [XREF_BIBR - XREF_BIBR]." + + + +
+ + + +
+ + + + + + 28298922 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to BCAR4 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In sum, BCAR4 associated with beta-catenin to prevent its degradation and then activates Wnt and beta-catenin signaling pathway." + + + +
+ + + +
+ + + + + + 29190958 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to adenomatous polyposis coli activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The isomerized beta-catenin could not bind to nuclear adenomatous polyposis coli, which drives beta-catenin out of the nucleus for proteasomal degradation, which consequently increases the retention of beta-catenin in the nucleus and might explain the decrease of beta-catenin ubiquitination." + + + +
+ + + +
+ + + + + + 26740630 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to BCL9 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "BCL9 interacts with beta-catenin and enhances Wnt and beta-catenin signaling." + + + +
+ + + +
+ + + + + + 26384318 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to APC activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Sec62 competitively disrupted the interaction between beta-catenin and APC to inhibit the beta-catenin destruction complex assembly." + + + +
+ + + +
+ + + + + + 33858476 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to TCF4E activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "TPA also increased the interaction between beta-catenin and TCF4E in a CK1epsilon and delta dependent way, and finally led to activation of the Wnt and beta-catenin pathway." + + + +
+ + + +
+ + + + + + 30038030 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 activates mutated CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Stabilizing mutations of beta-Catenin and increased levels of nuclear beta-Catenin have been reported in castration resistant PCa." + + + +
+ + + +
+ + + + + + 18218096 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to KRT19 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Linc-KILH enhanced the interaction between beta-catenin and KRT19 in cytoplasm and promoted the nuclear translocation of beta-catenin in HCC cells." + + + +
+ + + +
+ + + + + + 33767587 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to ESR1 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "estrogen receptor (ER) alpha- and beta-catenin precipitated within the same immunocomplexes, reciprocally enhanced the transactivation of cognate reporter genes, and were reciprocally recruited to cognate response elements in the promoters of endogenous target genes." + + + +
+ + + +
+ + + + + + 15304487 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Tyrosine-phosphorylated CTNNB1 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The release of tyrosine phosphorylated beta-catenin and Arm from adherens junctions increases the cytoplasmic pool of beta-catenin and Arm that is readily available, upon receiving a Wnt signal, for translocation to the nucleus, where it regulates transcription [XREF_BIBR, XREF_BIBR]." + + + +
+ + + +
+ + + + + + 25803041 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to FOXM1 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "FoxM1 also directly interacts with beta-catenin during glioma tumorigenesis to induce nuclear localization of beta-catenin, a clear indication of canonical Wnt signaling activation [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 25714027 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to TCF4 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Similarly, the interaction between nuclear beta-catenin and TCF-4 or LEF-1 was reduced by CaSR activation, indicating an inhibitory association of beta-catenin and TCF-4 or LEF-1 in the nucleus." + + + +
+ + + +
+ + + + + + 27108064 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to MUC1 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "In contrast, MUC1 has a highly conserved cytoplasmic tail, which binds beta-catenin, a key component of adherens junctions and a regulator of transcription, in a process that is tightly regulated by MUC1 phosphorylation." + + + +
+ + + +
+ + + + + + 12508284 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to CDK7 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Mechanistically, CDK7 interacted with beta-catenin, enhanced the interaction between beta-catenin and TCF4, and activated beta-catenin and TCF signaling." + + + +
+ + + +
+ + + + + + 29981747 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to lymphoid enhancer-binding factor activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Finally, beta-catenin interacts with T-cell factor and lymphoid enhancer binding factor (TCF/LEF) transcription factors and activates Wnt and beta-catenin target genes such as c-MYC and Cyclin D1 [28-31]." + + + +
+ + + +
+ + + + + + 23927962 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to KLF5 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "It is not known whether beta-catenin and KLF5 cooperatively or independently regulate cell proliferation, but KLF5 can physically interact with beta-catenin in COS-1 cells to enhance the nuclear localization and transcriptional activity of beta-catenin [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 25433271 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to TCF7L2 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The active beta-catenin binds with T-cell factor 4 (Tcf4) and activates beta-catenin and Tcf-dependent transcription." + + + +
+ + + +
+ + + + + + 17828298 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to LEF1 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Similarly, the interaction between nuclear beta-catenin and TCF-4 or LEF-1 was reduced by CaSR activation, indicating an inhibitory association of beta-catenin and TCF-4 or LEF-1 in the nucleus." + + + +
+ + + +
+ + + + + + 27108064 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to PBOV1 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In this study, we find that PBOV1 binds to beta-catenin to protect it from phosphorylating by GSK-3beta and thus activates Wnt and beta-catenin signaling, which resulted in markedly boosted stemness of HCC." + + + +
+ + + +
+ + + + + + 30143633 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Modified CTNNB1 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In the presence of WNT ligands, the beta-catenin destruction complex does not form, beta-catenin escapes ubiquitin-proteasome degradation and translocates to the nucleus to enable transcription of WNT and beta-catenin target genes." + + + +
+ + + +
+ + + + + + 29316982 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to DHX32 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Binding of DHX32 to beta-catenin prevented beta-catenin from ubiquitination and degradation, and therefore, enhanced the activity of beta-catenin." + + + +
+ + + +
+ + + + + + 28330603 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The activation of the canonical Wnt and beta-catenin signalling pathway involves the binding of a canonical Wnt ligand to the receptors ' frizzled ' (FZD) and low-density lipoprotein receptor related protein 5/6 (LRP5/6), thereby inhibiting beta-catenin phosphorylation, which allows beta-catenin to escape degradation and accumulate in the cytoplasm." + + + +
+ + + +
+ + + + + + 22901430 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to RXRalpha protein activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The research of the same group confirmed that retinol administration to ATRA resistant human CRC cells increased beta-catenin and RXRalpha protein interactions, inducing beta-catenin transport to the degradation location in the cytoplasm [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 33276489 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to SALL4B isoforms activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Furthermore, both SALL4A and SALL4B isoforms can bind beta-catenin protein and synergistically activate the Wnt and beta-catenin signaling pathway 65." + + + +
+ + + +
+ + + + + + 26892498 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to FOXP3 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Co-immunoprecipitation results further indicated that FOXP3 could physically interacted with beta-catenin and TCF4 to enhance the functions of beta-catenin and TCF4, inducing transcription of Wnt target genes to promote cell proliferation, invasion and EMT induction." + + + +
+ + + +
+ + + + + + 28716029 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Mutated CTNNB1 activates mutated CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "We showed that muscle overexpression of the Ctnnb1 mutant without the TAD was unable to rescue the presynaptic deficits of Ctnnb1 mutation, indicating that the transcription regulation is critical for muscle Ctnnb1 to control presynaptic differentiation." + + + +
+ + + +
+ + + + + + 26159615 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to PSEN1 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "They demonstrated that PSEN1 forms a complex with beta-catenin in vivo that increases beta-catenin stability." + + + +
+ + + +
+ + + + + + 18685724 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to TCF_LEF activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "ICAT has been reported to inhibit the interaction between beta-catenin and TCF and impaired the activation of beta-catenin and TCF signaling." + + + +
+ + + +
+ + + + + + 27829235 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Mutated CTNNB1 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "ACPs are driven by somatic mutations of CTNNB1, which causes the β-catenin pathway not to be degraded effectively, accumulates in cells, and further leads to overactivation of the Wnt-β-catenin pathway (24, 25)." + + + +
+ + + +
+ + + + + + 34660308 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to MUC1-C cytoplasmic domain activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The MUC1-C cytoplasmic domain binds directly to beta-catenin and thereby attenuates beta-catenin degradation." + + + +
+ + + +
+ + + + + + 21643558 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Phosphorylated CTNNB1 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The phosphorylated beta-catenin in the beta-catenin destruction complex is polyubiquitinated by beta-transducin repeat containing protein, a component of a ubiquitin ligase complex, targeting beta-catenin for rapid degradation by the proteasome." + + + +
+ + + +
+ + + + + + 25788321 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to GS26575 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Finally, the interaction between the transcription factor Forkhead box M1 and beta-catenin that promotes beta-catenin nuclear localization in tumor cells and maintains GIC self-renewal has been recently described [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 22400111 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to PAK1 activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "PAK1 also interacts with beta-catenin to promote beta-catenin and TCF4 activation in gastric epithelial cells and it phosphorylates beta-catenin at Serine 675, which increases the stability and transcriptional activity of beta-catenin in colon cancer cells XREF_BIBR." + + + +
+ + + +
+ + + + + + 27713506 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to YWHAZ activates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "14-3-3zeta Interacts with beta-Catenin and Activates beta-Catenin-Dependent Promoters in HEK293T cells and Colon Carcinoma cells. " + + + +
+ + + +
+ + + + + + 15492215 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + + + + + + +
+
+
CTNNB1 inhibits CTNNB1.
+
+
+ + + + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 42 + + + + + + +
+
+
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 bound to APC inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Under normal conditions, APC protein binds with beta-catenin together with axin and GSK-3beta thereby promoting proteolytic degradation of beta-catenin." + + + +
+ + + +
+ + + + + + 19779968 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to LEF1 inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Chibby, a newly identified β-catenin antagonist, can disrupt the association between β-catenin and LEF1, and promotes β-catenin nuclear export via a chibby-14-3-3-β-catenin complex [81,82]." + + + +
+ + + +
+ + + + + + 32961708 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to MSAB inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "MSAB binds to beta-catenin promoting its degradation, and specifically downregulates Wnt and beta-catenin target genes." + + + +
+ + + +
+ + + + + + 27320923 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to DHX32 inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Binding of DHX32 to beta-catenin prevented beta-catenin from ubiquitination and degradation, and therefore, enhanced the activity of beta-catenin." + + + +
+ + + +
+ + + + + + 28330603 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to IQGAP inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "IQGAP is localized to sites of cell-cell contact and negatively regulates adhesion by binding to beta-catenin, which causes beta-catenin to dissociate from alpha-catenin [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 21619876 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to PPP3 inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "39 We have shown that calcineurin independent NFAT5 binds beta-catenin and represses Wnt and beta-catenin signaling in HEK293 and human intestinal cells." + + + +
+ + + +
+ + + + + + 23764852 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to TBL1X inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "NCOR2, nuclear receptor corepressor 2 (also known as SMRT), mediates liver cancer cells of certain target genes.18, 20 Chao Qu etal20 have shown that NCOR2 can bind with TBL1 and TBLR1, which disrupts the binding of beta-catenin to TBL1 and TBLR1 complex, thereby inactivating the Wnt and beta-catenin pathway." + + + +
+ + + +
+ + + + + + 30680848 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to MUC1 inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Mutation of the SRM attenuated binding of MUC1 to beta-catenin and MUC1 mediated inhibition of beta-catenin degradation." + + + +
+ + + +
+ + + + + + 16288032 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to Cadherin inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Binding of beta-catenin to cadherin antagonizes beta-catenin signaling function by sequestering beta-catenin to the cadherin complex." + + + +
+ + + +
+ + + + + + 9199178 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to proteins inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "These two proteins interact with each other and bind to beta-catenin to promote proteasomal beta-catenin degradation that is independent of GSK3beta phosphorylation (XREF_FIG F)." + + + +
+ + + +
+ + + + + + 20064927 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to dnTCF4 construct inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The dnTCF4 construct competitively binds beta-catenin, preventing beta-catenin from associating with wild-type TCF4 to promote target gene transcription." + + + +
+ + + +
+ + + + + + 24256430 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to MUC1-CD inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Binding of MUC1-CD to beta-catenin suppresses the capacity of beta-catenin to interact with E-cadherin at adherens junctions, resulting in the loss of cell-cell adhesion, thus playing a relevant role in tumor invasion." + + + +
+ + + +
+ + + + + + 27602113 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to Peg3 inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Taken together, these data indicate that Peg3 and Pw1 binds with Siah1 and beta-catenin to promote beta-catenin degradation via a GSK3beta independent pathway." + + + +
+ + + +
+ + + + + + 20064927 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to KLF4 inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In addition, we suggest the existence of a dual mechanism whereby 5-ASA-mediated beta-catenin inhibition is caused by mu-protocadherin-dependent sequestration of beta-catenin to the plasma membrane and by the direct binding of KLF4 to beta-catenin." + + + +
+ + + +
+ + + + + + 29794245 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to AXIN inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Depletion of another Wnt antagonist, Dapper3, which colocalises with Dishevelled (Dvl) and forms a complex with cytoplasmic proteins Axin, glycogen synthase kinase-3 (GSK3), casein kinase 1 (CK1) and β-catenin causes the accumulation of Dvl2 and β-catenin and aggravates the fibrotic phenotype after UUO [105,106]." + + + +
+ + + +
+ + + + + + 32365994 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to TCF_LEF inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Binding of beta-catenin to TCF is prevented by ICAT (inhibitor of beta-catenin and TCF), which interacts with the central ARM repeat of beta-catenin, thereby blocking access to them." + + + +
+ + + +
+ + + + + + 26075748 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to CD133 inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Remarkably, the cytoplasmatic domain of CD133 binds beta-catenin and the downregulation of CD133 increases beta-catenin degradation and impairs tumor growth in vitro and in vivo [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 28412969 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to CTNNA inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In response to EGF stimulation, ERK2 activates phosphorylation of CK2, which phosphorylates alpha-catenin to disrupt the association between beta-catenin and alpha-catenin, thereby promoting transcriptional activation of beta-catenin for tumor cell invasion [2]." + + + +
+ + + +
+ + + + + + 27412911 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to FOXO3 inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In contrast, FOXO3a was reported to inhibit the expression beta-catenin by transactivating miR-34b/c in prostate cancer [XREF_BIBR], and FOXO3a can directly bind to beta-catenin and compete with T cell factor (TCF) for the interaction to beta-catenin, thereby inhibiting beta-catenin and TCF transcriptional activity [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 29361949 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to BTRC inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In summary, DHC could enhance the expression of BTRC and may also promote beta-catenin and BTRC binding, thus accelerating the ubiquitination degradation of beta-catenin." + + + +
+ + + +
+ + + + + + 33833997 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to CTNNBIP1 inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In the mechanism study, CARF was found to interact with beta-catenin, impaired the interaction between beta-catenin and ICAT, and activated beta-catenin and TCF signaling." + + + +
+ + + +
+ + + + + + 27829235 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to GSK3B inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "This, in turn, inhibits the binding of GSK3beta with MUC1-CT, which leads to better binding of MUC1-CT with beta-catenin and the inhibition of GSK3beta mediated degradation of beta-catenin." + + + +
+ + + +
+ + + + + + 20348949 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to SOX9 inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Sox9 binds to beta-catenin and inhibits the transcriptional activity of beta-catenin, in part through inducing beta-catenin degradation [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 21594584 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to VDR inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Interestingly, VDR and LXR can both directly bind to beta-catenin, thereby preventing beta-catenin from binding to its target sites." + + + +
+ + + +
+ + + + + + 27092172 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to TCF4 inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "However, the beta-catenin and TCF4 interaction was abolished by E-cadherin and correlated with its nuclear localization, and consequently decreased beta-catenin and TCF4 transcriptional activity." + + + +
+ + + +
+ + + + + + 26075748 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to FLYWCH1 inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Using a modified yeast-2-hybrid based Ras-Recruitment system, it is demonstrated that FLYWCH1 directly binds to unphosphorylated (nuclear) beta-catenin efficiently suppressing the transcriptional activity of Wnt and beta-catenin signaling that can not be rescued by TCF4." + + + +
+ + + +
+ + + + + + 30097457 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to NFAT5 inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Our data suggest that NFAT5 interacts with beta-catenin, thus repressing Wnt and beta-catenin activation." + + + +
+ + + +
+ + + + + + 23764852 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to sox17b.1 inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "To investigate how the beta-catenin and XSox17beta interaction could inhibit beta-catenin and TCF activity, we mapped the XSox17beta binding site on beta-catenin." + + + +
+ + + +
+ + + + + + 10549281 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to HIC1 and TCF4 inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "This appears to be due to the ability of HIC1 to associate with TCF-4 and to recruit TCF-4 and beta-catenin to the HIC1 bodies." + + + +
+ + + +
+ + + + + + 16724116 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to TCF3 inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "A fragment of beta-catenin and a peptide encoding the NH 2 terminus of Tcf4 that block the interaction between beta-catenin and Tcf3 stimulate beta-catenin degradation, indicating this interaction normally plays an important role in regulating beta-catenin turnover." + + + +
+ + + +
+ + + + + + 11524435 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to PRKCA inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "However, protein protein interactions between PKCalpha and beta-catenin exist under conditions of glucose deprivation, which suggests that glucose deprivation may enhance the interaction affinity between PKCalpha and beta-catenin to promote the degradation of beta-catenin." + + + +
+ + + +
+ + + + + + 25691573 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to CDH1 inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In CAC, E-cadherin forms a complex with beta-catenin and in combination with the actin cytoskeleton prevents nuclear translocation of beta-catenin, thus regulating the activity of the Wnt and catenin signaling pathways [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 28145888 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 inhibits ubiquitinated CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Each cell line was treated with increasing concentrations of retinol for 24 or 48 h. Retinol reduced beta-catenin protein levels and increased ubiquitinated beta-catenin in all cell lines." + + + +
+ + + +
+ + + + + + 17219422 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 inhibits phosphorylated CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The level of intracellular beta-catenin is regulated by AKT substrate GSK3beta, which phosphorylates beta-catenin and promotes ubiquitin-proteasome degradation of the phosphorylated beta-catenin [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 27783993 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to PCDHGA9 inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Our results suggest that PCDHGA9 might interact with beta-catenin to prevent beta-catenin from dissociating in the cytoplasm and translocating to the nucleus." + + + +
+ + + +
+ + + + + + 29348665 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "This observation is not surprising, given that GSK-3beta is known to play an essential role in the canonical Wnt signal-transduction pathway, initiating proteasomal degradation of beta-catenin by phosphorylating beta-catenin on key residues." + + + +
+ + + +
+ + + + + + 21743491 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to PEG3 inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Taken together, these data indicate that Peg3 and Pw1 binds with Siah1 and beta-catenin to promote beta-catenin degradation via a GSK3beta independent pathway." + + + +
+ + + +
+ + + + + + 20064927 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Phosphorylated CTNNB1 inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Then, inhibition of beta-catenin phosphorylation raises the levels of beta-catenin in the cell and allows beta-catenin to enter the nuclei to bind to the transcription factor TCF/LEF, thereby initiating transcription of downstream target genes [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 33712069 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to SIRT2 inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "We presented evidence that SIRT2 interacts with beta-catenin, deacetylates and suppresses beta-catenin from becoming active." + + + +
+ + + +
+ + + + + + 24866770 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to AMER1 inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Amer1 and WTX, in addition to its role in mediating receptor signaling, can bind beta-catenin, Axin, APC, and beta-TRCP to stimulate beta-catenin degradation in cultured mammalian cells and Xenopus egg extract." + + + +
+ + + +
+ + + + + + 23256519 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to RXRA inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Using both mammalian two-hybrid assay in vivo and immunoprecipitation in vitro we found that retinoid X receptor alpha (RXR alpha) directly interacted with beta-catenin and suppressed beta-catenin transcription activity and protein expression in colorectal cancer cells." + + + +
+ + + +
+ + + + + + 18196974 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to TRIM33 inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Our novel findings demonstrate that prolonged Wnt stimulation can lead to activation of PKCdelta; then, phosphorylation of beta-catenin at Ser715 by activated PKCdelta facilitates the interaction between TRIM33 and beta-catenin, which induce beta-catenin degradation and hence shut down Wnt signaling." + + + +
+ + + +
+ + + + + + 25639486 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to LXR inhibits CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Interestingly, VDR and LXR can both directly bind to beta-catenin, thereby preventing beta-catenin from binding to its target sites." + + + +
+ + + +
+ + + + + + 27092172 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + + + + + + +
+
+
CTNNB1 phosphorylates CTNNB1.
+
+
+ + + + + + + + + + + + + + 4 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 3 + + + + + + 19 + + + + + + +
+
+
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 phosphorylates CTNNB1 on Y489. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Using a library of human normal and diseased human lung samples, we identified a distinct signature of nuclear accumulation of beta-catenin phosphorylated at tyrosine 489 and epithelial cell cytosolic localization of beta-catenin phosphorylated at tyrosine 654 in early normal lung development and fibrotic lung diseases BPD and IPF." + + + +
+ + + +
+ + + + + + 29355514 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Phosphorylated CTNNB1 phosphorylates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "While beta-catenin is continuously phosphorylated by kinases, phosphorylated beta-catenin released from the kinase complex is instantaneously reversed by PP2A." + + + +
+ + + +
+ + + + + + 19061640 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 phosphorylates CTNNB1 on S715. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In vitro kinase assays demonstrate that constitutively active PKCδ directly phosphorylates WT β-catenin but not β-catenin S715A. Phosphorylation of β-catenin at Ser715 is also detected by a specific antibody, which is abolished by depletion of PKCδ." + + + +
+ + + +
+ + + + + + 32723561 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 leads to the phosphorylation of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Hence, Caco-2 cells harbor an APC mutation, whereas HCT-116 cells harbor a single amino acid deletion (CTNNB1 p.S45del) which prevent beta-catenin phosphorylation and degradation by the proteasome." + + + +
+ + + +
+ + + + + + 26107817 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1-S37A leads to the phosphorylation of CTNNB1 on S33. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Finally, phosphorylation resistance mutants of beta-catenin (S33F, S37A, and T41A) that had abolished GSK3beta dependent phosphorylation of beta-catenin at Ser 33 or -37 and Thr 41, which is required for beta-catenin degradation, were also employed in analysis." + + + +
+ + + +
+ + + + + + 25691573 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 phosphorylates CTNNB1 on S37. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Phosphorylation of beta-catenin by glycogen synthase kinase (GSK)-3beta at Ser33 and Ser37 and Thr47 targets beta-catenin for ubiquitination and proteosomal degradation XREF_BIBR." + + + +
+ + + +
+ + + + + + 21935365 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 phosphorylates CTNNB1 on S33. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In the absence of Wnt signaling, the beta-catenin destruction complex continuously phosphorylates beta-catenin protein at Ser 33, 37, 45 and Thr 41 to target beta-catenin for degradation via an ubiquitin dependent pathway XREF_BIBR, XREF_BIBR, XREF_BIBR." + + + +
+ + + +
+ + + + + + 25003522 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 leads to the phosphorylation of CTNNB1 on S45. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Interestingly, Wnt5a was recently proposed to promote beta-catenin and E-cadherin association via CK1alpha mediated phosphorylation of beta-catenin at Ser45 but not Ser33 XREF_BIBR which supports a role for Ser45 phospho-beta-catenin in cell adhesion and also raises the possibility that localised phosphorylation at individual sites may lead to distinct functional outcomes." + + + +
+ + + +
+ + + + + + 21152425 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 phosphorylates CTNNB1 at position 45. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In the absence of Wnt signaling, the beta-catenin destruction complex continuously phosphorylates beta-catenin protein at Ser 33, 37, 45 and Thr 41 to target beta-catenin for degradation via an ubiquitin dependent pathway XREF_BIBR, XREF_BIBR, XREF_BIBR." + + + +
+ + + +
+ + + + + + 25003522 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Unphosphorylated CTNNB1 phosphorylates CTNNB1 on S552. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Total beta-catenin, de-phosphorylated beta-catenin (canonical activation, de-phospho beta-catenin) and phosphorylated beta-catenin at Ser 552 (non canonical activation, p-Ser 552 beta-catenin) levels were determined in primary human dermal fibroblasts, cytosol and nucleus, by western blot analysis and fluorescence microscopy, before and after stimulation by A 2A receptor selective agonist CGS21680, with and without A 2A receptor selective antagonist (SCH56261) pretreatment." + + + +
+ + + +
+ + + + + + 27595240 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Modified CTNNB1 leads to the phosphorylation of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "These natural products have been found to inhibit the beta-catenin signaling through different molecular mechanisms (XREF_FIG), including, but not limited to, 1) down-regulating beta-catenin expression, 2) modulating beta-catenin phosphorylation, 3) promoting beta-catenin protein degradation, 4) inhibiting beta-catenin nuclear translocation, and others." + + + +
+ + + +
+ + + + + + 32695004 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 phosphorylated on S33 phosphorylates CTNNB1 on S33. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The phosphorylationof beta-catenin on Ser33, Ser37 or Thr41 induces its ubiquitination and subsequent degradation by the proteosome.22 The total beta-catenin and phosphorylated beta-catenin levels both increased after exposed to 2500-micro strain tension after 3, 6, and 18 h." + + + +
+ + + +
+ + + + + + 30897979 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 phosphorylated on S552 leads to the phosphorylation of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "A number of recent reports showed that the phosphorylation of beta-catenin on ser552 by PKA enhances the transcriptional ability of beta-catenin independent of the phosphorylation of beta-catenin in the N-terminal domain at canonical sites regulated by Wnt pathway [XREF_BIBR, XREF_BIBR]." + + + +
+ + + +
+ + + + + + 25866509 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 phosphorylates CTNNB1 on S473. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "We used the following antibodies in the present study : Akt, pAkt (Ser 473), E-cadherin, N-cadherin, beta-catenin, phosphorylated beta-catenin (Ser33/37/Thr41), pERK (Tyr 204), GAPDH, MCP-1, Snail and Twist (Santa Cruz Biotechnology, Santa Cruz, CA)." + + + +
+ + + +
+ + + + + + 21855541 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 phosphorylated on S45 leads to the phosphorylation of CTNNB1 on T41. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "It is established that Ser45 phosphorylation by casein kinase I (CKI) initiates phosphorylation at Thr41, Ser37, and Ser33 by glycogen synthase kinase 3 (GSK3) and that phosphorylated Ser37 and Ser33 are recognized by the F-box protein beta-TrCP, a component of a ubiquitin ligase complex that mediates beta-catenin degradation." + + + +
+ + + +
+ + + + + + 16618120 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 phosphorylates CTNNB1 on Y142. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "To address the possibility that phosphorylation of β-catenin at Y142 modulates the extent to which MET and β-catenin functionally interact, neocortical neurons were transfected with wild-type β-catenin that can be phosphorylated at Y142 with HGF treatment ( xref ) or a mutant form of β-catenin that cannot be phosphorylated at Y142 (β-cateninY142F; xref )." + + + +
+ + + +
+ + + + + + 27595133 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 leads to the phosphorylation of CTNNB1 on S552. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Taken together, our results suggest TNF activates beta-catenin through the AKT mediated phosphorylation of beta-catenin (Ser552) rather than via Wnt upregulation." + + + +
+ + + +
+ + + + + + 28345588 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Modified CTNNB1 leads to the phosphorylation of CTNNB1 on Y654. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Indeed, phosphorylation of beta-catenin on tyrosine 654 was enhanced by the co-overexpression of FAK and beta-catenin in mouse livers (XREF_FIG)." + + + +
+ + + +
+ + + + + + 31069844 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 acetylated on K49 leads to the phosphorylation of CTNNB1 on S45. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "Our results in the human NPCs are supportive of this latter model as HDAC6 inhibition-induced increase in Lys49 acetylation was accompanied by increase in Ser45 phosphorylation but increased Ser45 phosphorylation was not accompanied by increased phosphorylation of Ser33, Ser37, and Thr41." + + + +
+ + + +
+ + + + + + 25546293 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 phosphorylated on S45 leads to the phosphorylation of CTNNB1 on S37. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "It is established that Ser45 phosphorylation by casein kinase I (CKI) initiates phosphorylation at Thr41, Ser37, and Ser33 by glycogen synthase kinase 3 (GSK3) and that phosphorylated Ser37 and Ser33 are recognized by the F-box protein beta-TrCP, a component of a ubiquitin ligase complex that mediates beta-catenin degradation." + + + +
+ + + +
+ + + + + + 16618120 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 leads to the phosphorylation of CTNNB1 on threonine. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In the absence of Wnt ligand, Axin contributes to the formation of beta-catenin destruction complex, which leads to phosphorylation of beta-catenin on serine and threonine residues near its N-terminus providing beta-catenin a target for ubiquitination and rendering it to ubiquitin dependent proteasome mediated degradation [XREF_BIBR, XREF_BIBR, XREF_BIBR]." + + + +
+ + + +
+ + + + + + 28445439 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 phosphorylates CTNNB1 on S675. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Consistent with our observation in the HL-60 cell line, GSK3β inhibition with BRD3731 at 20 μM decreased β-catenin S33/37/T41 phosphorylation and induced β-catenin S675 phosphorylation resulting in increased β-catenin." + + + +
+ + + +
+ + + + + + 29515000 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 leads to the phosphorylation of CTNNB1 on serine. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Activation of PKC-alpha inhibited beta-catenin response transcription by down-regulation of intracellular beta-catenin and induced phosphorylation of the N-terminal serine and threonine residues (Ser33/Ser37/Thr41) of beta-catenin, marking it for proteasomal degradation, in colon cancer cells." + + + +
+ + + +
+ + + + + + 20141613 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 phosphorylates CTNNB1 on T41. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In the absence of Wnt signaling, the beta-catenin destruction complex continuously phosphorylates beta-catenin protein at Ser 33, 37, 45 and Thr 41 to target beta-catenin for degradation via an ubiquitin dependent pathway XREF_BIBR, XREF_BIBR, XREF_BIBR." + + + +
+ + + +
+ + + + + + 25003522 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 leads to the phosphorylation of CTNNB1 on tyrosine. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Ron and beta-catenin associate and Ron kinase activity leads to tyrosine phosphorylation of beta-catenin." + + + +
+ + + +
+ + + + + + 21423209 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 phosphorylated on S45 leads to the phosphorylation of CTNNB1 on S33. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "It is established that Ser45 phosphorylation by casein kinase I (CKI) initiates phosphorylation at Thr41, Ser37, and Ser33 by glycogen synthase kinase 3 (GSK3) and that phosphorylated Ser37 and Ser33 are recognized by the F-box protein beta-TrCP, a component of a ubiquitin ligase complex that mediates beta-catenin degradation." + + + +
+ + + +
+ + + + + + 16618120 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + + + + + + +
+
+
CTNNB1 increases the amount of CTNNB1.
+
+
+ + + + + + + + + + + + + + 4 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 22 + + + + + + +
+
+
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 phosphorylated on amino acid 44 increases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "XREF_BIBR - XREF_BIBR CK2 has been previously reported to phosphorylate beta-catenin at Thr393, 44 which increases beta-catenin expression via ubiquitin-proteasome system and activates Wnt signaling pathway." + + + +
+ + + +
+ + + + + + 33602894 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to CDH1 increases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Alternatively, the interaction between E-cadherin and beta-catenin at the adherens junction raises the intriguing possibility that the loss of E-cadherin function may actively regulate the levels of free beta-catenin, thereby altering its ability to regulate target genes that support tumor invasion." + + + +
+ + + +
+ + + + + + 12810698 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Modified CTNNB1 increases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "On the other hand, overexpression of beta-catenin in shDKK1-transfectants restored the transcription of beta-catenin, and attenuated the inhibitory effect of shDKK1 on invasion." + + + +
+ + + +
+ + + + + + 24325363 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1-S45F increases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Our results showed that the transfection of CTNNB1 T41A or S45F mutation had no effect on the expression of total beta-catenin; however, the transfection of CTNNB1 S45F mutation induced the nuclear expression of beta-catenin, suggesting that this specific mutation might affect beta-catenin translocation to the nucleus independent of cell type." + + + +
+ + + +
+ + + + + + 32651460 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 increases the amount of phosphorylated CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "To test if the S33F mutation in beta-catenin increases the amount of non phosphorylated beta-catenin in cells, we measured the amount of total and non phosphorylated beta-catenin using cell fractionation followed by Western blotting." + + + +
+ + + +
+ + + + + + 29872041 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Tyrosine-phosphorylated CTNNB1 increases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Contrary to phosphorylation on S33/S37/T41, beta-catenin tyrosine phosphorylation on Y86 is enhanced in CEACAM1 low cell populations exhibiting comparable total nuclear beta-catenin levels." + + + +
+ + + +
+ + + + + + 27572314 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to factor increases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Then, beta-catenin is carried into the nucleus and forms a complex with T cell factor and lymphocyte enhancer factors (TCF/LEF) to activate the expression of beta-catenin responsive genes, such as c-Jun, cyclin-D1, c-Myc, and peroxisome proliferator activated receptor-delta [8-10]." + + + +
+ + + +
+ + + + + + 27568288 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Acetylated CTNNB1 increases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In addition, because acetylation of beta-catenin can enhance the transcription of beta-catenin, increase in acetylation of beta-catenin could enhance the expression of beta-catenin." + + + +
+ + + +
+ + + + + + 29069825 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 acetylated on K49 increases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "Upon HDAC6 inhibition, Ac- Lys49 β-catenin levels increased in NPCs, which was accompanied by increased membrane localization of β-catenin." + + + +
+ + + +
+ + + + + + 25546293 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to enhancer factors increases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Then, beta-catenin is carried into the nucleus and forms a complex with T cell factor and lymphocyte enhancer factors (TCF/LEF) to activate the expression of beta-catenin responsive genes, such as c-Jun, cyclin-D1, c-Myc, and peroxisome proliferator activated receptor-delta [8-10]." + + + +
+ + + +
+ + + + + + 27568288 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 increases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In addition, kirenol up-regulated the expression of beta-catenin, CCND1, ALP, and ColA1 which were down-regulated by siRNA knockdown of beta-catenin." + + + +
+ + + +
+ + + + + + 25062891 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Unphosphorylated CTNNB1 increases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Dephosphorylation of beta-Catenin does not inactivate beta-Catenin but actually prevents proteasomal degradation and increases cellular levels of beta-Catenin." + + + +
+ + + +
+ + + + + + 21092273 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to hTcf-4 nuclear increases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The results are in concordance with previous studies where beta-catenin protein levels have been found to be downregulated XREF_BIBR and the beta-catenin and hTcf -4 nuclear complex reduced XREF_BIBR upon Zn stimulation in HT29-APC cells indicating, decreased levels of nuclear beta-catenin." + + + +
+ + + +
+ + + + + + 21437251 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to lef increases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In the nucleus, beta-catenin binds and activates the transcription factor LEF and TCF to initiate the transcription of Wnt and beta-catenin target genes." + + + +
+ + + +
+ + + + + + 30551901 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Mutated CTNNB1 increases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Mutation of beta-catenin, APC or Axin found in several human cancers was reported to cause elevated beta-catenin levels and yield inappropriate activation of TCF target genes such as c-Myc and cyclin D1, which associate with cell neoplastic transformation [1,2]." + + + +
+ + + +
+ + + + + + 19563778 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1-S33Y increases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "From mutations file" + + + +
+ + + +
+ + + + + + 9671767 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to YWHAZ increases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "We show that one of them, 14-3-3zeta, enhances beta-catenin-dependent transcription by maintaining a high level of beta-catenin protein in the cytoplasm." + + + +
+ + + +
+ + + + + + 15492215 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1-K180R increases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The consequent depletion of SET7/9 by shRNA or the mutation of the beta-catenin (K180R) significantly enhanced the expression of Wnt and beta-catenin target genes such as c-myc and cyclin D1 and promoted the growth of cancer cells." + + + +
+ + + +
+ + + + + + 26116705 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to ASF1A increases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Mechanistically, ASF1A interacted with beta-catenin and promoted the transcription of beta-catenin target genes including c-MYC, cyclin D1, ZEB1 and LGR5, thereby stimulating proliferation, stemness and migration and invasion of GIC cells." + + + +
+ + + +
+ + + + + + 28625518 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to TCF_LEF increases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In the nucleus, beta-catenin binds and activates the transcription factor LEF and TCF to initiate the transcription of Wnt and beta-catenin target genes." + + + +
+ + + +
+ + + + + + 30551901 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1-T41A increases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "From mutations file" + + + +
+ + + +
+ + + + + + 11170292 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to RORalpha increases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The inhibition is accomplished through binding of RORalpha to beta-catenin, which suppresses the transcription of Wnt and beta-catenin target genes." + + + +
+ + + +
+ + + + + + 23443091 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to PKD1 increases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "We demonstrate that PKD1 directly interacts with beta-catenin and attenuates beta-catenin transcriptional activity by decreasing nuclear beta-catenin levels." + + + +
+ + + +
+ + + + + + 25149539 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Phosphorylated CTNNB1 increases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "37 Mutations in the beta-catenin phosphorylation region can activate beta-catenin signaling by upholding cellular beta-catenin levels." + + + +
+ + + +
+ + + + + + 29188076 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 phosphorylated on serine and an unknown residue increases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In our study, in both NFs and KFs, treatment with Wnt5a induced a significant increase in the total beta-catenin level but not the phosphorylated beta-catenin levels at serine 45 and threonine 41 positions, where it is phosphorylated by casein kinase 1a to undergo degradation." + + + +
+ + + +
+ + + + + + 23471552 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 phosphorylated on S552 increases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Phosphorylation of beta-catenin at S552 by AKT has also been found to enhance beta-catenin protein levels and nuclear signaling by standard reporter assays, although the precise mechanism remains unclear." + + + +
+ + + +
+ + + + + + 19623618 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + + + + + + +
+
+
CTNNB1 dephosphorylates CTNNB1.
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 19 + + + + + + +
+
+
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 phosphorylated on S33 leads to the dephosphorylation of CTNNB1 on S33. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In addition, recent studies have shown evidence for inhibition of Wnt/Akt signaling in T24 cells by an active synthetic APF derivative including decreased phosphorylation of Akt, GSK3β, and β-catenin ser45/thr41, with increased phosphorylation of β-catenin ser33,37/thr41 [28]." + + + +
+ + + +
+ + + + + + 24900993 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1-S33F leads to the dephosphorylation of CTNNB1 on S33. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Finally, phosphorylation resistance mutants of beta-catenin (S33F, S37A, and T41A) that had abolished GSK3beta dependent phosphorylation of beta-catenin at Ser 33 or -37 and Thr 41, which is required for beta-catenin degradation, were also employed in analysis." + + + +
+ + + +
+ + + + + + 25691573 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 phosphorylated on S33 leads to the dephosphorylation of CTNNB1 phosphorylated on S33 on S33. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In addition, recent studies have shown evidence for inhibition of Wnt/Akt signaling in T24 cells by an active synthetic APF derivative including decreased phosphorylation of Akt, GSK3β, and β-catenin ser45/thr41, with increased phosphorylation of β-catenin ser33,37/thr41 [28]." + + + +
+ + + +
+ + + + + + 24900993 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Mutated CTNNB1 leads to the dephosphorylation of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Activating somatic mutations in the β-catenin gene (CTNNB1 coding) on chromosome 3p occur in almost 100% of SPNs (10), where CTNNB1 mutations disrupt the phosphorylation and degradation of the β-catenin protein." + + + +
+ + + +
+ + + + + + 34733780 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 leads to the dephosphorylation of CTNNB1 on threonine. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Activation of PKC-alpha inhibited beta-catenin response transcription by down-regulation of intracellular beta-catenin and induced phosphorylation of the N-terminal serine and threonine residues (Ser33/Ser37/Thr41) of beta-catenin, marking it for proteasomal degradation, in colon cancer cells." + + + +
+ + + +
+ + + + + + 20141613 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Modified CTNNB1 leads to the dephosphorylation of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Functional studies showed that the activation of NF-kappaB transcriptional activity in mutant osteoblasts resulted in increased beta-catenin phosphorylation, reduced osteoblast beta-catenin expression, and altered expression of Wnt and beta-catenin target genes." + + + +
+ + + +
+ + + + + + 26060255 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 dephosphorylates CTNNB1 on Y86. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "As shown in Fig. 3 A, SHP-1 expression markedly inhibited c-src and CA-induced beta-catenin and TCF transcriptional activity.Because SHP-1 can dephosphorylate residues Y86 and Y654 on the beta-catenin protein, these residues were therefore mutated into phenylalanine and the transcriptional activity of the subsequent beta catenin mutants analyzed : beta-catenin and Y86F, beta-catenin and Y654F and beta-catenin/Y86F/Y654F." + + + +
+ + + +
+ + + + + + 20840866 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 methylated on K49 leads to the dephosphorylation of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "For instance, lnc-beta-Catm recruits EZH2 to catalyze K49 methylation of beta-catenin which inhibits phosphorylation and ubiquitination of beta-catenin and promotes its stability [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 33672592 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 phosphorylated on S33 leads to the dephosphorylation of CTNNB1 on T41. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In addition, recent studies have shown evidence for inhibition of Wnt/Akt signaling in T24 cells by an active synthetic APF derivative including decreased phosphorylation of Akt, GSK3β, and β-catenin ser45/thr41, with increased phosphorylation of β-catenin ser33,37/thr41 [28]." + + + +
+ + + +
+ + + + + + 24900993 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 phosphorylated on S33 leads to the dephosphorylation of CTNNB1 on S45. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In addition, recent studies have shown evidence for inhibition of Wnt/Akt signaling in T24 cells by an active synthetic APF derivative including decreased phosphorylation of Akt, GSK3β, and β-catenin ser45/thr41, with increased phosphorylation of β-catenin ser33,37/thr41 [28]." + + + +
+ + + +
+ + + + + + 24900993 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1-T41A leads to the dephosphorylation of CTNNB1 on S33. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Finally, phosphorylation resistance mutants of beta-catenin (S33F, S37A, and T41A) that had abolished GSK3beta dependent phosphorylation of beta-catenin at Ser 33 or -37 and Thr 41, which is required for beta-catenin degradation, were also employed in analysis." + + + +
+ + + +
+ + + + + + 25691573 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 leads to the dephosphorylation of CTNNB1 on tyrosine. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Loss of linkage between the cell-cell adhesion molecule E-cadherin and the actin cytoskeleton, that is mediated by a three protein link of beta-catenin, alpha-catenin and alpha-actinin, is induced by association of the EGF receptor having the protein tyrosine kinase activity with beta-catenin that leads to tyrosine phosphorylation of beta-catenin and concomitant dissociation of alpha-catenin from it [XREF_BIBR, XREF_BIBR]." + + + +
+ + + +
+ + + + + + 11716783 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 phosphorylated on S33 leads to the dephosphorylation of CTNNB1 phosphorylated on S33 on S45. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In addition, recent studies have shown evidence for inhibition of Wnt/Akt signaling in T24 cells by an active synthetic APF derivative including decreased phosphorylation of Akt, GSK3β, and β-catenin ser45/thr41, with increased phosphorylation of β-catenin ser33,37/thr41 [28]." + + + +
+ + + +
+ + + + + + 24900993 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 leads to the dephosphorylation of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In the absence of Wnt signals, this multi protein complex promotes degradation of free beta-catenin via GSK3beta mediated phosphorylation of specific beta-catenin residues; phosphorylated beta-catenin is subsequently ubiquitinated and degraded by the proteasome." + + + +
+ + + +
+ + + + + + 19886711 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 phosphorylated on S33 leads to the dephosphorylation of CTNNB1 phosphorylated on S33 on T41. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In addition, recent studies have shown evidence for inhibition of Wnt/Akt signaling in T24 cells by an active synthetic APF derivative including decreased phosphorylation of Akt, GSK3β, and β-catenin ser45/thr41, with increased phosphorylation of β-catenin ser33,37/thr41 [28]." + + + +
+ + + +
+ + + + + + 24900993 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 leads to the dephosphorylation of CTNNB1 on S45. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "After treated with ATRA, transcriptional activity of beta-catenin decreased by downregulating phosphorylation of beta-catenin Ser45, Y654 and GSK-3beta Ser9." + + + +
+ + + +
+ + + + + + 26902198 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1-S37F leads to the dephosphorylation of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Next, we tested 501Mel melanoma cells, which harbor an endogenous CTNNB1 S37F mutation preventing beta-catenin phosphorylation and degradation (Rubinfeld et al., 1997)." + + + +
+ + + +
+ + + + + + 30008323 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 leads to the dephosphorylation of CTNNB1 on Y654. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "After treated with ATRA, transcriptional activity of beta-catenin decreased by downregulating phosphorylation of beta-catenin Ser45, Y654 and GSK-3beta Ser9." + + + +
+ + + +
+ + + + + + 26902198 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Modified CTNNB1 leads to the dephosphorylation of CTNNB1 on S675. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "PhosphoS675 beta-catenin levels were again inhibited by H89, confirming that PKA is involved in beta-catenin S675 phosphorylation." + + + +
+ + + +
+ + + + + + 21307168 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + + + + + + +
+
+
CTNNB1 decreases the amount of CTNNB1.
+
+
+ + + + + + + + + + + + + + 4 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 12 + + + + + + +
+
+
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 bound to PTK6 decreases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "PTK6 can directly associate with beta-catenin and inhibit beta-catenin and TCF regulated transcription." + + + +
+ + + +
+ + + + + + 22989419 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Modified CTNNB1 decreases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "It was proposed that high beta-catenin levels blocked NF-kappaB-mediated cell apoptosis and LPS induced NF-kappaB promoted beta-catenin expression and beta-catenin-regulated proliferation in APC mutated or depleted cells where beta-catenin degradation was compromised." + + + +
+ + + +
+ + + + + + 27713747 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 phosphorylated on T41 decreases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "It is known that Ser33, Ser37, and Thr41 are phosphorylated by GSK3β, which creates the binding site for β-TrCP and subsequent ubiquitination by the E3 ubiquitin ligase system.[6,7]" + + + +
+ + + +
+ + + + + + 25546293 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to RORalpha decreases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Additionally, RORalpha binds to beta-catenin that suppresses Wnt and beta-catenin gene transcription, known to be an important pathway in breast cancer cell adhesion and cell growth." + + + +
+ + + +
+ + + + + + 29497051 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to DECT decreases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "These findings are consistent with our previous observations that DECT interacts with beta-catenin, reduces the level of beta-catenin associated with endogenous cadherins, and inhibits cell surface localization of endogenous cadherins when expressed in cells." + + + +
+ + + +
+ + + + + + 26453620 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Phosphorylated CTNNB1 decreases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Then, inhibition of beta-catenin phosphorylation raises the levels of beta-catenin in the cell and allows beta-catenin to enter the nuclei to bind to the transcription factor TCF/LEF, thereby initiating transcription of downstream target genes [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 33712069 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 phosphorylated on S45 decreases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "cyclin-CDK2 demonstrate beta-catenin phosphorylation on residues Ser(33), Ser(37), Thr(41), and Ser(45). This phosphorylation promotes rapid degradation of cytosolic beta-catenin" + + + +
+ + + +
+ + + + + + 14985333 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to TCF/LEF decreases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The phosphorylation and degradation of beta-catenin is then inhibited, followed by beta-catenin accumulation in cytoplasm and translocation into nucleus, where the binding of beta-catenin to TCF/LEF induces expression of Wnt and beta-catenin target gene [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 29383202 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to retinoic acid receptor decreases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Recently it was reported that beta-catenin interacts with retinoic acid receptor in a retinoid dependent manner, reducing beta-catenin and TCF regulated transcription." + + + +
+ + + +
+ + + + + + 14514656 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to NF2 decreases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "We discovered that Merlin physically interacts with beta-catenin, alters the sub-cellular localization of beta-catenin, and significantly reduces the protein levels of beta-catenin by targeting it for degradation through the upregulation of Axin1." + + + +
+ + + +
+ + + + + + 26908451 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 phosphorylated on S37 decreases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "It is known that Ser33, Ser37, and Thr41 are phosphorylated by GSK3β, which creates the binding site for β-TrCP and subsequent ubiquitination by the E3 ubiquitin ligase system.[6,7]" + + + +
+ + + +
+ + + + + + 25546293 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 decreases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "E2F1 is a potent and specific inhibitor of beta-catenin and T-cell factor (TCF)-dependent transcription, and E2F1 deregulation suppresses beta-catenin activity in an adenomatous polyposis coli (APC)/GSK3-independent manner, reducing the expression of key beta-catenin targets XREF_BIBR." + + + +
+ + + +
+ + + + + + 28042322 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 phosphorylated on S33 decreases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "It is known that Ser33, Ser37, and Thr41 are phosphorylated by GSK3β, which creates the binding site for β-TrCP and subsequent ubiquitination by the E3 ubiquitin ligase system.[6,7]" + + + +
+ + + +
+ + + + + + 25546293 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Ubiquitinated CTNNB1 decreases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Furthermore, IKKalpha interacted with beta-catenin and mediated beta-catenin stabilization by inhibiting beta-catenin ubiquitination, which in turn stimulated beta-catenin and Tcf-dependent transcription 41 Second, IKKalpha but not IKKbeta, induces CyclinD1 expression, which is identified as a target of Wnt and beta-catenin signaling pathway, also through Tcf activity." + + + +
+ + + +
+ + + + + + 21686046 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to NEK2 decreases the amount of ubiquitinated CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Thus the interaction of Nek2 and beta-catenin does not require Nek2 activity, occurs in the absence of beta-catenin phosphorylation, and decreases the level of ubiquitinated beta-catenin." + + + +
+ + + +
+ + + + + + 24501426 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to FERMT1 decreases the amount of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Investigations of underlying mechanisms found that FERMT1 interacted directly with beta-catenin and activated the Wnt and beta-catenin signaling pathway by decreasing the phosphorylation level of beta-catenin, enhancing beta-catenin nuclear translocation and increasing the transcriptional activity of beta-catenin/TCF/LEF." + + + +
+ + + +
+ + + + + + 27641329 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + + + + + + +
+
+
CTNNB1 ubiquitinates CTNNB1.
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 5 + + + + + + +
+
+
+ + + +
+
+ + + + + +
+
+
+ Phosphorylated CTNNB1 leads to the ubiquitination of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The destruction complex regulates the sequential phosphorylation of beta-catenin, which leads to the polyubiquitination of beta-catenin by beta-TrCP and subsequent degradation by the proteasome pathway." + + + +
+ + + +
+ + + + + + 29789528 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 ubiquitinates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Axin-1 is a key protein component of the Wnt signaling pathway [XREF_BIBR] acting as a scaffolding protein, assembling the beta-catenin destruction complex that phosphorylates and subsequently polyubiquitinates beta-catenin [XREF_BIBR - XREF_BIBR]." + + + +
+ + + +
+ + + + + + 28355271 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 phosphorylated on S37 leads to the ubiquitination of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "PKA has been shown to phosphorylate GSK3alpha and beta at Ser21 and Ser9, respectively, thus activating beta-catenin signaling by preventing GSK3 from phosphorylating beta-catenin at Ser33, Ser37 and Thr41, which leads to beta-catenin ubiquitination and destruction XREF_BIBR." + + + +
+ + + +
+ + + + + + 27313491 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Mutated CTNNB1 leads to the ubiquitination of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In CRC cells, the APC and β-catenin mutations not only prevent this normal β-catenin phosphorylation and ubiquitination but also promote abnormal β-catenin stabilization, translocation, and nuclear accumulation (Liu et al., 1999, 2002; Yang et al., 2006)." + + + +
+ + + +
+ + + + + + 33305174 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Modified CTNNB1 leads to the ubiquitination of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The levels of cytoplasmic beta-catenin are normally controlled by a multi-proteins destruction complex to promote phosphorylation of beta-catenin, which is required to trigger ubiquitination of beta-catenin and its subsequent degradation by proteasomes." + + + +
+ + + +
+ + + + + + 24015932 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + + + + + + +
+
+
CTNNB1 deubiquitinates CTNNB1.
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 4 + + + + + + +
+
+
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 leads to the deubiquitination of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In the mammalian WNT signaling pathway, for example, phosphorylation of beta-catenin by PKA is known to inhibit the ubiquitination of beta-catenin promoted by CKI and glycogen Synthetase kinase 3 beta (GSK-3 beta) phosphorylation [XREF_BIBR, XREF_BIBR]." + + + +
+ + + +
+ + + + + + 26198228 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Phosphorylated CTNNB1 leads to the deubiquitination of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Inactivation of GSK3beta results to inability of beta-catenin phosphorylation, which would decrease the ubiquitination and proteolysis of beta-catenin." + + + +
+ + + +
+ + + + + + 29541202 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 methylated on K49 leads to the deubiquitination of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "For instance, lnc-beta-Catm recruits EZH2 to catalyze K49 methylation of beta-catenin which inhibits phosphorylation and ubiquitination of beta-catenin and promotes its stability [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 33672592 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Methylated CTNNB1 leads to the deubiquitination of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "EZH2 methylates beta-catenin to suppress the ubiquitination of beta-catenin, thereby allowing beta-catenin to activate Wnt signaling to sustain the self-renewal of HCC CSCs [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 33808647 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + + + + + + +
+
+
CTNNB1 acetylates CTNNB1.
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + 1 + + + + + + +
+
+
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 leads to the acetylation of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "As also shown in +Figure 7A +, Aspirin caused a marked increase in acetylated β-catenin (Lys-49) but a slight increase in GSK-3β, whereas LiCl caused a slight decrease in acetylated β-catenin but a marked decrease in GSK-3β." + + + +
+ + + +
+ + + + + + 31824307 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 acetylates CTNNB1 on K49. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Since β-catenin can be acetylated at K49 by CREB-binding protein (CBP) and Ac-K49 β-catenin is required for activation of Wnt target genes, xref – xref we detected the Ac-K49 β-catenin level when Bcl-3 was silenced." + + + +
+ + + +
+ + + + + + 32355204 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + + + + + + +
+
+
CTNNB1 methylates CTNNB1.
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 methylates CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "We found that nuclear beta-catenin as well as endogenously methylated beta-catenin (both in the cytoplasm and nucleus) in these two cell lines was significantly decreased by SMYD2 knockdown." + + + +
+ + + +
+ + + + + + 28915556 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + + + + + + +
+
+
CTNNB1 deacetylates CTNNB1.
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 leads to the deacetylation of CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "It was found that HIF-1alpha binds hARD1 through the oxygen dependent degradation domain and, in so doing, dissociates hARD1 from beta-catenin, which prevents beta-catenin acetylation." + + + +
+ + + +
+ + + + + + 18593917 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + +
+
+
+
+
+ + + + + + + + +
+
+
CTNNB1
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+ + + + + + + + +
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 binds CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "These different subtypes of ovarian cancer are associated with different molecular characteristics: high grade serous cancers typically contain TP53 mutations [ xref , xref ], low grade serous carcinomas often have RAS-RAF pathway activation and mutations in the KRAS and BRAF genes [ xref ], low-grade endometrioid cancers are associated with mutations in the beta-catenin gene, CTNNB1 [ xref ], and mucinous cancers frequently have mutations in KRAS [ xref ]." + + + +
+ + + +
+ + + + + + 18208621 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "These different subtypes of ovarian cancer are associated with different molecular characteristics: high grade serous cancers typically contain TP53 mutations [ xref , xref ], low grade serous carcinomas often have RAS-RAF pathway activation and mutations in the KRAS and BRAF genes [ xref ], low-grade endometrioid cancers are associated with mutations in the beta-catenin gene, CTNNB1 [ xref ], and mucinous cancers frequently have mutations in KRAS [ xref ]." + + + +
+ + + +
+ + + + + + 18208621 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + +
+
+
+
+
+ + + + + + + + +
+
+
ZNF148 affects CTNNB1
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+ + + + + + + + +
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 binds CTNNB1 and ZNF148. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Subsequently, sustained levels of CTNNB1 expression can be maintained through the binding of ZBP-89 protein to the CTNNB1 promoter further expanding the pool of β–catenin protein." + + + +
+ + + +
+ + + + + + 27758879 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds CTNNB1 and ZNF148. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Subsequently, sustained levels of CTNNB1 expression can be maintained through the binding of ZBP-89 protein to the CTNNB1 promoter further expanding the pool of β–catenin protein." + + + +
+ + + +
+ + + + + + 27758879 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + +
+
+
+
+
+ + + + + + + + +
+
+
Wnt affects CTNNB1
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+ + + + + + + + +
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 binds CTNNB1 and Wnt. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Apart from this, we also predicted that hsa-miR-516a-3p down-regulates CTNNB1 gene, also known as beta-catenin, which is associated with WNT signalling for SCs renewal xref ." + + + +
+ + + +
+ + + + + + 25475098 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds CTNNB1 and Wnt. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Apart from this, we also predicted that hsa-miR-516a-3p down-regulates CTNNB1 gene, also known as beta-catenin, which is associated with WNT signalling for SCs renewal xref ." + + + +
+ + + +
+ + + + + + 25475098 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + +
+
+
+
+
+ + + + + + + + +
+
+
TCF_LEF affects CTNNB1
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+ + + + + + + + +
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 binds TCF_LEF and CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "A naturally occurring 9 kDa protein, called inhibitor of β-catenin and TCF (ICAT), binds β-catenin and prevents its interaction with TCF1 [ xref , xref ] and thereby inhibits TCF1 and β-catenin-dependent gene expression [ xref ]." + + + +
+ + + +
+ + + + + + 20082155 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds TCF_LEF and CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "A naturally occurring 9 kDa protein, called inhibitor of β-catenin and TCF (ICAT), binds β-catenin and prevents its interaction with TCF1 [ xref , xref ] and thereby inhibits TCF1 and β-catenin-dependent gene expression [ xref ]." + + + +
+ + + +
+ + + + + + 20082155 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + +
+
+
+
+
+ + + + + + + + +
+
+
PETE affects CTNNB1
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+ + + + + + + + +
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 binds PETE and CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Furthermore, the increase of PCa growth was associated with decreased phospho-β-catenin expression and increased total β-catenin expression." + + + +
+ + + +
+ + + + + + 24088787 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds PETE and CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Furthermore, the increase of PCa growth was associated with decreased phospho-β-catenin expression and increased total β-catenin expression." + + + +
+ + + +
+ + + + + + 24088787 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + +
+
+
+
+
+ + + + + + + + +
+
+
LRP5 affects CTNNB1
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+ + + + + + + + +
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 binds CTNNB1 and LRP5. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We found that BMP-2 treatment at 12, 24, and 48 hours increased the active form of nuclear β-catenin protein levels (Figure xref ), decreased phospho-β-catenin protein levels (Figure xref ), and significantly upregulated LRP-5 mRNA and protein expression, but not LRP-6 ( P < 0.05; Figure xref and xref )." + + + +
+ + + +
+ + + + + + 22513174 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds CTNNB1 and LRP5. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We found that BMP-2 treatment at 12, 24, and 48 hours increased the active form of nuclear β-catenin protein levels (Figure xref ), decreased phospho-β-catenin protein levels (Figure xref ), and significantly upregulated LRP-5 mRNA and protein expression, but not LRP-6 ( P < 0.05; Figure xref and xref )." + + + +
+ + + +
+ + + + + + 22513174 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + +
+
+
+
+
+ + + + + + + + +
+
+
GNAS affects CTNNB1
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+ + + + + + + + +
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 binds CTNNB1 and GNAS. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "2 + This study demonstrates that aberrant nuclear localization of β-catenin is significantly associated with CTNNB1 exon 3 mutations." + + + +
+ + + +
+ + + + + + 11238046 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds CTNNB1 and GNAS. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "2 + This study demonstrates that aberrant nuclear localization of β-catenin is significantly associated with CTNNB1 exon 3 mutations." + + + +
+ + + +
+ + + + + + 11238046 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + +
+
+
+
+
+ + + + + + + + +
+
+
CTNNB1 affects ZNF148
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+ + + + + + + + +
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 binds CTNNB1 and ZNF148. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Subsequently, sustained levels of CTNNB1 expression can be maintained through the binding of ZBP-89 protein to the CTNNB1 promoter further expanding the pool of β–catenin protein." + + + +
+ + + +
+ + + + + + 27758879 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds CTNNB1 and ZNF148. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Subsequently, sustained levels of CTNNB1 expression can be maintained through the binding of ZBP-89 protein to the CTNNB1 promoter further expanding the pool of β–catenin protein." + + + +
+ + + +
+ + + + + + 27758879 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + +
+
+
+
+
+ + + + + + + + +
+
+
CTNNB1 affects Wnt
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+ + + + + + + + +
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 binds CTNNB1 and Wnt. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Apart from this, we also predicted that hsa-miR-516a-3p down-regulates CTNNB1 gene, also known as beta-catenin, which is associated with WNT signalling for SCs renewal xref ." + + + +
+ + + +
+ + + + + + 25475098 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds CTNNB1 and Wnt. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Apart from this, we also predicted that hsa-miR-516a-3p down-regulates CTNNB1 gene, also known as beta-catenin, which is associated with WNT signalling for SCs renewal xref ." + + + +
+ + + +
+ + + + + + 25475098 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + +
+
+
+
+
+ + + + + + + + +
+
+
CTNNB1 affects TCF_LEF
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+ + + + + + + + +
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 binds TCF_LEF and CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "A naturally occurring 9 kDa protein, called inhibitor of β-catenin and TCF (ICAT), binds β-catenin and prevents its interaction with TCF1 [ xref , xref ] and thereby inhibits TCF1 and β-catenin-dependent gene expression [ xref ]." + + + +
+ + + +
+ + + + + + 20082155 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds TCF_LEF and CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "A naturally occurring 9 kDa protein, called inhibitor of β-catenin and TCF (ICAT), binds β-catenin and prevents its interaction with TCF1 [ xref , xref ] and thereby inhibits TCF1 and β-catenin-dependent gene expression [ xref ]." + + + +
+ + + +
+ + + + + + 20082155 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + +
+
+
+
+
+ + + + + + + + +
+
+
CTNNB1 affects PETE
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+ + + + + + + + +
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 binds PETE and CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Furthermore, the increase of PCa growth was associated with decreased phospho-β-catenin expression and increased total β-catenin expression." + + + +
+ + + +
+ + + + + + 24088787 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds PETE and CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Furthermore, the increase of PCa growth was associated with decreased phospho-β-catenin expression and increased total β-catenin expression." + + + +
+ + + +
+ + + + + + 24088787 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + +
+
+
+
+
+ + + + + + + + +
+
+
CTNNB1 affects LRP5
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+ + + + + + + + +
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 binds CTNNB1 and LRP5. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We found that BMP-2 treatment at 12, 24, and 48 hours increased the active form of nuclear β-catenin protein levels (Figure xref ), decreased phospho-β-catenin protein levels (Figure xref ), and significantly upregulated LRP-5 mRNA and protein expression, but not LRP-6 ( P < 0.05; Figure xref and xref )." + + + +
+ + + +
+ + + + + + 22513174 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds CTNNB1 and LRP5. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We found that BMP-2 treatment at 12, 24, and 48 hours increased the active form of nuclear β-catenin protein levels (Figure xref ), decreased phospho-β-catenin protein levels (Figure xref ), and significantly upregulated LRP-5 mRNA and protein expression, but not LRP-6 ( P < 0.05; Figure xref and xref )." + + + +
+ + + +
+ + + + + + 22513174 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + +
+
+
+
+
+ + + + + + + + +
+
+
CTNNB1 affects GNAS
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+ + + + + + + + +
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 binds CTNNB1 and GNAS. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "2 + This study demonstrates that aberrant nuclear localization of β-catenin is significantly associated with CTNNB1 exon 3 mutations." + + + +
+ + + +
+ + + + + + 11238046 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds CTNNB1 and GNAS. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "2 + This study demonstrates that aberrant nuclear localization of β-catenin is significantly associated with CTNNB1 exon 3 mutations." + + + +
+ + + +
+ + + + + + 11238046 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + +
+
+
+
+
+ + + + + + + + +
+
+
CTNNB1 affects AXIN2
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+ + + + + + + + +
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 binds CTNNB1 and AXIN2. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Nuclear β-catenin phosphorylated at tyrosine 489 associated with an increased expression of Wnt target gene AXIN2, suggesting that the observed β-catenin signature is of functional significance during normal development and injury repair." + + + +
+ + + +
+ + + + + + 29355514 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds CTNNB1 and AXIN2. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Nuclear β-catenin phosphorylated at tyrosine 489 associated with an increased expression of Wnt target gene AXIN2, suggesting that the observed β-catenin signature is of functional significance during normal development and injury repair." + + + +
+ + + +
+ + + + + + 29355514 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + +
+
+
+
+
+ + + + + + + + +
+
+
CTNNB1 affects APC
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+ + + + + + + + +
+ + + +
+
+ + + + + +
+
+
+ APC binds CTNNB1 and CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Alteration of β-catenin signaling caused by mutation in the APC or CTNNB1 gene is associated with colorectal tumorigenesis [ xref ]." + + + +
+ + + +
+ + + + + + 21764279 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ APC binds CTNNB1 and CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Alteration of β-catenin signaling caused by mutation in the APC or CTNNB1 gene is associated with colorectal tumorigenesis [ xref ]." + + + +
+ + + +
+ + + + + + 21764279 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + +
+
+
+
+
+ + + + + + + + +
+
+
AXIN2 affects CTNNB1
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+ + + + + + + + +
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 binds CTNNB1 and AXIN2. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Nuclear β-catenin phosphorylated at tyrosine 489 associated with an increased expression of Wnt target gene AXIN2, suggesting that the observed β-catenin signature is of functional significance during normal development and injury repair." + + + +
+ + + +
+ + + + + + 29355514 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds CTNNB1 and AXIN2. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Nuclear β-catenin phosphorylated at tyrosine 489 associated with an increased expression of Wnt target gene AXIN2, suggesting that the observed β-catenin signature is of functional significance during normal development and injury repair." + + + +
+ + + +
+ + + + + + 29355514 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + +
+
+
+
+
+ + + + + + + + +
+
+
APC affects CTNNB1
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+ + + + + + + + +
+ + + +
+
+ + + + + +
+
+
+ APC binds CTNNB1 and CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Alteration of β-catenin signaling caused by mutation in the APC or CTNNB1 gene is associated with colorectal tumorigenesis [ xref ]." + + + +
+ + + +
+ + + + + + 21764279 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ APC binds CTNNB1 and CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Alteration of β-catenin signaling caused by mutation in the APC or CTNNB1 gene is associated with colorectal tumorigenesis [ xref ]." + + + +
+ + + +
+ + + + + + 21764279 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + +
+
+
+
+
+ + + +
+
+ + + + \ No newline at end of file diff --git a/notebooks/beta_catenin_dou/analysis_output/DKK4_statements.html b/notebooks/beta_catenin_dou/analysis_output/DKK4_statements.html new file mode 100644 index 000000000..9e314f25a --- /dev/null +++ b/notebooks/beta_catenin_dou/analysis_output/DKK4_statements.html @@ -0,0 +1,2803 @@ + + + + + + + + + + + + Statements for DKK4 + + + + + + + + + + + + + + + + + + + + + + + + + + +
+ + + + + + + +
+ + +
+
+
+

+ Statements +

+
+
+ +
+
+ + + +
+ +
+ + + + databases + + + + + + psp + + + + + + cbn + + + + + + pc + + + + + + bel_lc + + + + + + signor + + + + + + biogrid + + + + + + tas + + + + + + hprd + + + + + + trrust + + + + + + ctd + + + + + + vhn + + + + + + pe + + + + + + drugbank + + + + + + omnipath + + + + + + conib + + + + + + crog + + + + + + dgi + + + + + + minerva + + + + + + creeds + + + + + + ubibrowser + + + + + + acsn + + + + + + + + | + +
| + + + + + + geneways + + + + + + tees + + + + + + gnbr + + + + + + semrep + + + + + + isi + + + + + + trips + + + + + + rlimsp + + + + + + medscan + + + + + + eidos + + + + + + sparser + + + + + + reach + + + + + reading + + + +
+
+ + + +
+
+ + + + + + + + +
+
+
+ + + +
+ + + + + + + + +
+
+
CTNNB1 activates DKK4.
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 7 + + + + + + +
+
+
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 activates DKK4. + + 7 / 7 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 7 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Thus, even though DKK-4 has previously been considered a Wnt " antagonist " similar to the 1,25D-upregulated DKK-1 gene, the fact that DKK-4 is both targeted and upregulated by beta-catenin, and is significantly elevated in colonic tumor tissue [XREF_BIBR, XREF_BIBR] suggests that DKK-4 may in fact possess unique tumorigenic properties." + + + +
+ + + +
+ + + + + + 20043299 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Calcitriol also represses expression of DKK4 in SW480-ADH cells; DKK4 is induced by the TCF7L2 and CTNNB1 pathway and enhances the migratory, invasive and pro angiogenic potential of colorectal cancer." + + + +
+ + + +
+ + + + + + 27245104 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "DICKKOPF-4 is induced by TCF and betacatenin and upregulated in human colon cancer, promotes tumour cell invasion and angiogenesis and is repressed by 1alpha,25-dihydroxyvitamin D3." + + + +
+ + + +
+ + + + + + 20367197 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Stabilization of beta-catenin reverses the proliferation suppressive effect of DKK4 in HCC cells cultured in NG." + + + +
+ + + +
+ + + + + + 27272409 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Furthermore, the relationship between glucose and DKK4 became apparent because stabilization of beta-catenin by inhibiting GSK3beta under normoglycemic condition causes abrogation of DKK4 functionality thereby facilitating cellular proliferation." + + + +
+ + + +
+ + + + + + 27272409 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "DICKKOPF-4 is induced by TCF and beta-catenin and upregulated in human colon cancer, promotes tumour cell invasion and angiogenesis and is repressed by 1alpha,25-dihydroxyvitamin D3." + + + +
+ + + +
+ + + + + + 18408752 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "However, DKK4, induced by beta-catenin activation, was found to be upregulated and promote invasion and angiogenesis in human colon cancers [XREF_BIBR, XREF_BIBR]." + + + +
+ + + +
+ + + + + + 28666421 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + + + + + + +
+
+
CTNNB1 binds DKK4.
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 2 + + + + + + 2 + + + + + + +
+
+
+ + + +
+
+ + + + + +
+
+
+ DKK4 binds CTNNB1. + + 4 / 4 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 2 + + + + + + 2 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Moreover, 1,25 D, but not LCA, suppressed endogenous expression of the beta-catenin target gene DKK-4 independent of VDR DNA binding activity." + + + +
+ + + +
+ + + + + + 20043299 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "n Caco-2 colorectal cancer cells [XREF_BIBR], 1,25 D suppresses beta-catenin transcriptional activity and endogenous expression of the beta-catenin target gene DKK-4 independent of VDR DNA binding activity." + + + +
+ + + +
+ + + + + + 22085499 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Furthermore, immunohistochemical studies showed that decreased expression of DKK4 was associated with β-catenin accumulation in HCC tissues." + + + +
+ + + +
+ + + + + + 22249261 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We found that several proteins involved in Wnt signaling, including DKK4 and β-catenin, and proteins that bind β-catenin, such as FUS and NONO, were up-regulated in SPNs." + + + +
+ + + +
+ + + + + + 26148796 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + + + + + + +
+
+
CTNNB1 increases the amount of DKK4.
+
+
+ + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 increases the amount of DKK4. + + 2 / 2 + + +
+
+
+ + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+ + + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 17397822 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "TPA dramatically increased DKK4 promoter transcription mediated by beta-catenin and TCF4E or beta-catenin/TCF4E/CK1epsilon." + + + +
+ + + +
+ + + + + + 30038030 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + + + + + + +
+
+
CTNNB1 decreases the amount of DKK4.
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 decreases the amount of DKK4. + + 0 / 0 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + +
+
+
+
+
+ + + +
+
+ + + + \ No newline at end of file diff --git a/notebooks/beta_catenin_dou/analysis_output/FABP4_statements.html b/notebooks/beta_catenin_dou/analysis_output/FABP4_statements.html new file mode 100644 index 000000000..d0d22ebba --- /dev/null +++ b/notebooks/beta_catenin_dou/analysis_output/FABP4_statements.html @@ -0,0 +1,1259 @@ + + + + + + + + + + + + Statements for FABP4 + + + + + + + + + + + + + + + + + + + + + + + + + + +
+ + + + + + + +
+ + +
+
+
+

+ Statements +

+
+
+ +
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+ + + +
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+ + + + databases + + + + + + psp + + + + + + cbn + + + + + + pc + + + + + + bel_lc + + + + + + signor + + + + + + biogrid + + + + + + tas + + + + + + hprd + + + + + + trrust + + + + + + ctd + + + + + + vhn + + + + + + pe + + + + + + drugbank + + + + + + omnipath + + + + + + conib + + + + + + crog + + + + + + dgi + + + + + + minerva + + + + + + creeds + + + + + + ubibrowser + + + + + + acsn + + + + + + + + | + +
| + + + + + + geneways + + + + + + tees + + + + + + gnbr + + + + + + semrep + + + + + + isi + + + + + + trips + + + + + + rlimsp + + + + + + medscan + + + + + + eidos + + + + + + sparser + + + + + + reach + + + + + reading + + + +
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+ + + + + + + + +
+
+
+ + + +
+ + + + + + + + +
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 decreases the amount of FABP4. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Beta-Catenin siRNA rescued the reduced expressions of PPARgamma, C/EBPalpha, fatty acid binding protein 4 and lipoprotein lipase by baicalin." + + + +
+ + + +
+ + + + + + 20627088 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + +
+
+
+
+
+ + + +
+
+ + + + \ No newline at end of file diff --git a/notebooks/beta_catenin_dou/analysis_output/GLCE_statements.html b/notebooks/beta_catenin_dou/analysis_output/GLCE_statements.html new file mode 100644 index 000000000..aa7efd3fd --- /dev/null +++ b/notebooks/beta_catenin_dou/analysis_output/GLCE_statements.html @@ -0,0 +1,1432 @@ + + + + + + + + + + + + Statements for GLCE + + + + + + + + + + + + + + + + + + + + + + + + + + +
+ + + + + + + +
+ + +
+
+
+

+ Statements +

+
+
+ +
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+ + + +
+ +
+ + + + databases + + + + + + psp + + + + + + cbn + + + + + + pc + + + + + + bel_lc + + + + + + signor + + + + + + biogrid + + + + + + tas + + + + + + hprd + + + + + + trrust + + + + + + ctd + + + + + + vhn + + + + + + pe + + + + + + drugbank + + + + + + omnipath + + + + + + conib + + + + + + crog + + + + + + dgi + + + + + + minerva + + + + + + creeds + + + + + + ubibrowser + + + + + + acsn + + + + + + + + | + +
| + + + + + + geneways + + + + + + tees + + + + + + gnbr + + + + + + semrep + + + + + + isi + + + + + + trips + + + + + + rlimsp + + + + + + medscan + + + + + + eidos + + + + + + sparser + + + + + + reach + + + + + reading + + + +
+
+ + + +
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+ + + + + + + + +
+
+
+ + + +
+ + + + + + + + +
+ + + +
+
+ + + + + +
+
+
+ Modified CTNNB1 increases the amount of GLCE. + + 2 / 2 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 2 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "However, ectopic expression of TCF4 and beta-catenin was not sufficient to activate GLCE expression in MCF7 cells, suggesting that chromatin structure plays a key role in GLCE regulation." + + + +
+ + + +
+ + + + + + 22805760 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "However, ectopic expression of TCF4 and beta-catenin was not sufficient to activate GLCE expression in MCF7 cells, suggesting that chromatin structure plays a key role in GLCE regulation." + + + +
+ + + +
+ + + + + + | PMC + + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 increases the amount of GLCE. + + 0 / 0 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + +
+
+
+
+
+ + + +
+
+ + + + \ No newline at end of file diff --git a/notebooks/beta_catenin_dou/analysis_output/LEF1_explanations.html b/notebooks/beta_catenin_dou/analysis_output/LEF1_explanations.html new file mode 100644 index 000000000..f9b5b67ff --- /dev/null +++ b/notebooks/beta_catenin_dou/analysis_output/LEF1_explanations.html @@ -0,0 +1,2948 @@ + + + + + + + + + + + + INDRA Results + + + + + + + + + + + + + + + + + + + + + + + + + + +
+ + + + + + + +
+ + +
+
+
+

+ Statements +

+
+
+ +
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+ + + +
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| + + + + + + geneways + + + + + + tees + + + + + + gnbr + + + + + + semrep + + + + + + isi + + + + + + trips + + + + + + rlimsp + + + + + + medscan + + + + + + eidos + + + + + + sparser + + + + + + reach + + + + + reading + + + +
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+ + + +
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+ + + + + + + + +
+
+
+ + + +
+ + + + + + + + +
+ + + +
+
+ + + + + +
+
+
+ LEF1 decreases the amount of PLA2G4A. + + 2 / 2 + + +
+
+
+ + + + + + + + + + + + 2 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+ + + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + +
+
+
+ + + +
+
+
+ + + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ LEF1 decreases the amount of ACSL5. + + 2 / 2 + + +
+
+
+ + + + + + + + + + + + 2 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+ + + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + +
+
+
+ + + +
+
+
+ + + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ LEF1 decreases the amount of VWA2. + + 2 / 2 + + +
+
+
+ + + + + + + + + + + + 2 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+ + + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + +
+
+
+ + + +
+
+
+ + + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ LEF1 decreases the amount of CEMIP2. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+ + + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ LEF1 decreases the amount of RCN2. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+ + + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ LEF1 increases the amount of DKK4. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+ + + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 17397822 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ LEF1 decreases the amount of EPHA7. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+ + + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ LEF1 decreases the amount of CTNNA2. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+ + + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ LEF1 decreases the amount of VSNL1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+ + + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ LEF1 decreases the amount of FABP4. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+ + + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + +
+
+
+
+
+ + + +
+
+ + + + \ No newline at end of file diff --git a/notebooks/beta_catenin_dou/analysis_output/LEF1_statements.html b/notebooks/beta_catenin_dou/analysis_output/LEF1_statements.html new file mode 100644 index 000000000..fa592b42d --- /dev/null +++ b/notebooks/beta_catenin_dou/analysis_output/LEF1_statements.html @@ -0,0 +1,65629 @@ + + + + + + + + + + + + Statements for LEF1 + + + + + + + + + + + + + + + + + + + + + + + + + + +
+ + + + + + + +
+ + +
+
+
+

+ Statements +

+
+
+ +
+
+ + + +
+ +
+ + + + databases + + + + + + psp + + + + + + cbn + + + + + + pc + + + + + + bel_lc + + + + + + signor + + + + + + biogrid + + + + + + tas + + + + + + hprd + + + + + + trrust + + + + + + ctd + + + + + + vhn + + + + + + pe + + + + + + drugbank + + + + + + omnipath + + + + + + conib + + + + + + crog + + + + + + dgi + + + + + + minerva + + + + + + creeds + + + + + + ubibrowser + + + + + + acsn + + + + + + + + | + +
| + + + + + + geneways + + + + + + tees + + + + + + gnbr + + + + + + semrep + + + + + + isi + + + + + + trips + + + + + + rlimsp + + + + + + medscan + + + + + + eidos + + + + + + sparser + + + + + + reach + + + + + reading + + + +
+
+ + + +
+
+ + + + + + + + +
+
+
+ + + +
+ + + + + + + + +
+
+
CTNNB1 binds LEF1.
+
+
+ + + + + + + + + + + + + + 3 + + + + + + 3 + + + + + + 20 + + + + + + + + 4 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + 2 + + + + + + + + + + + + 405 + + + + + + 311 + + + + + + +
+
+
+ + + +
+
+ + + + + +
+
+
+ LEF1 binds CTNNB1. + + 622 / 622 + + +
+
+
+ + + + + + + + + + + + + + 3 + + + + + + 3 + + + + + + 20 + + + + + + + + 3 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + 2 + + + + + + + + + + + + 281 + + + + + + 310 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Combined with the established role of the Wnt signaling pathway in adult hippocampal neurogenesis together with the known association between Lef1 and beta-catenin, our results here suggest that Lef1 is an important part of the Wnt controlled regulation of neural precursor function in the adult dentate gyrus." + + + +
+ + + +
+ + + + + + 25565948 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In vertebrates, the conserved Wnt signalling cascade promotes the stabilization and nuclear accumulation of β-catenin, which then associates with the lymphoid enhancer factor/T cell factor proteins (LEF/TCFs) to activate target genes." + + + +
+ + + +
+ + + + + + 20126258 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Because it has been reported that LEF-1 interacts with beta-catenin outside the amino-terminal domain, namely, in the middle part of the molecule, the possible participation of beta-catenin has not been formally ruled out." + + + +
+ + + +
+ + + + + + 29998192 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Despite the finding that transcription factor LEF-1 interacts with beta-catenin to activate their target genes, such as EMT related gene SNAI2 XREF_BIBR, and induces EMT, we found that not only full-length LEF-1 but also LEF-1 lacking the N-terminal beta-catenin-binding domain can induce EMT." + + + +
+ + + +
+ + + + + + 29998192 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Undegraded beta-catenin in SPNs forms a complex with LEF1, enters the nucleus and activates transcription of several oncogenes including cyclin-D1 that is overexpressed in 70-100% of SPNs [XREF_BIBR, XREF_BIBR, XREF_BIBR]." + + + +
+ + + +
+ + + + + + 27267993 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Because it has been reported that LEF-1 interacts with β-catenin outside the amino-terminal domain, namely, in the middle part of the molecule, the possible participation of β-catenin has not been formally ruled out." + + + +
+ + + +
+ + + + + + 29998192 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Nonetheless, there is a report that in addition to the well-established amino-terminal β-catenin–binding domain of LEF-1, β-catenin binds to another site of LEF-1: residues 150–175 xref ." + + + +
+ + + +
+ + + + + + 29998192 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In our previous study, we have reported that not only wild-type LEF-1 but also an amino terminus–deleted mutant LEF-1, ΔNLEF-1, which cannot interact with β-catenin, has an ability to induce EMT xref ." + + + +
+ + + +
+ + + + + + 29998192 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Despite the finding that transcription factor LEF-1 interacts with β-catenin to activate their target genes, such as EMT-related gene SNAI2 xref , and induces EMT, we found that not only full-length LEF-1 but also LEF-1 lacking the N-terminal β-catenin–binding domain can induce EMT." + + + +
+ + + +
+ + + + + + 29998192 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In the nucleus, beta-catenin binds TCF and LEF1 transcription factors and drives the expression of specific target genes that control cellular processes ranging from proliferation to cell differentiation." + + + +
+ + + +
+ + + + + + 25124032 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "ILK has been shown to regulate cell fate via nuclear interaction of beta-catenin with lymphoid enhancer factor (LEF-1) transcription factors." + + + +
+ + + +
+ + + + + + 15673299 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Given the ability of DeltaNDeltaCbetacatenin to act in a dominant negative fashion in interfering with the activity of functional Lef1 and betacatenin complexes in keratinocytes in vitro, we then turned towards using this transgene to assess the consequences of diminished Wnt signaling on hair organogenesis and postnatal cycling." + + + +
+ + + +
+ + + + + + 12135986 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "These structures were accompanied by aberrant TOPGAL activation, reflective of functional Lef1 and beta-catenin complexes (XREF_FIG C)." + + + +
+ + + +
+ + + + + + 12135986 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In addition, CK2 has been shown to regulate the interaction and transactivation activity of a beta-catenin and LEF -1 complex through phosphorylation of LEF-1 at S42, S61 [XREF_BIBR; XREF_BIBR]." + + + +
+ + + +
+ + + + + + 19565571 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Beta-catenin forms complexes with Tcf and Lef-1 and functions as a transcriptional activator downstream of the Wnt signaling pathway." + + + +
+ + + +
+ + + + + + 9721853 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The Lef1, high mobility group (HMG) family transcription factor, interacts with beta-catenin and is a nuclear effector of Wnt1." + + + +
+ + + +
+ + + + + + 26537192 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Matrix metalloproteinase (s) mediate (s) NO induced dissociation of beta-catenin from membrane bound E-cadherin and formation of nuclear beta-catenin and LEF -1 complex." + + + +
+ + + +
+ + + + + + 12507936 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The use of this type of library has identified erythropoieitin (EPO) mimetics (promote EPO receptor dimerization), inhibitors of Myc and Max dimerization, inhibitors of LEF-1 and beta-catenin dimerization, inhibitors of the binding of the protease MMP-2 to alphavbeta3 integrin, and inhibitors of HIV protease." + + + +
+ + + +
+ + + + + + 21183197 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The association of Ep-ICD with FHL2 and Wnt pathway components - β-catenin and Lef-1 forms a nuclear complex that binds DNA at Lef-1 consensus sites and induces gene transcription, leading to increased cell proliferation and has been shown to be oncogenic in immunodeficient mice [ xref ]." + + + +
+ + + +
+ + + + + + 20579375 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In the nucleus, beta-catenin binds to TCF-4 and LEF-1 to produce a transcription factor complex, which mediates cell proliferation and epithelial-mesenchymal transition (EMT) by influencing genes [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 30867651 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The coordinated binding of beta-catenin and LEF-1 to enhancers is reminiscent of the cooperative binding of recombinant LEF-1 and beta-catenin proteins on chromatin templates in vitro." + + + +
+ + + +
+ + + + + + 25936800 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Because Wnt3a preferentially induces the full-length form of LEF-1, which includes the N-terminal beta-catenin interaction domain, this mechanism ensures mutually interdependent binding of LEF-1 and beta-catenin to chromatin and enables rapid and synchronous activation of downstream target genes." + + + +
+ + + +
+ + + + + + 25936800 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Beta-catenin is then accumulated in the cytoplasm and translocated to the nucleus and binds to transcription factors LEF-1 and TCF to regulate the transcription of downstream target genes." + + + +
+ + + +
+ + + + + + 22172041 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We conclude that Wnt3a signaling stimulates the robust assembly of LEF-1:β-catenin complexes near hESC mesendodermal genes." + + + +
+ + + +
+ + + + + + 25936800 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "As expected, Wnt3a greatly increased binding of both LEF-1 and β-catenin, predominantly to pre-existing enhancer sites." + + + +
+ + + +
+ + + + + + 25936800 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The coordinated binding of β-catenin and LEF-1 to enhancers is reminiscent of the cooperative binding of recombinant LEF-1 and β-catenin proteins on chromatin templates in vitro ( xref )." + + + +
+ + + +
+ + + + + + 25936800 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Because Wnt3a preferentially induces the full-length form of LEF-1 ( xref ), which includes the N-terminal β-catenin interaction domain, this mechanism ensures mutually interdependent binding of LEF-1 and β-catenin to chromatin and enables rapid and synchronous activation of downstream target genes." + + + +
+ + + +
+ + + + + + 25936800 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In the nucleus β-catenin associates with members of the Lymphoid Enhancing Factor/ T-cell Factor (LEF/TCF) family of transcription factors, and induces the expression of genes that regulate cell proliferation, differentiation, migration, genetic stability and apoptosis [57–60] ." + + + +
+ + + +
+ + + + + + 27090017 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Because EpICD has been shown to form β-catenin-mediated transcription complexes with LEF1 that is also overexpressed in endometrial tumors ( xref ), we examined LEF1 binding profiles in RL95-2 cells by ChIP-seq ( xref )." + + + +
+ + + +
+ + + + + + 27569206 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "These results suggest that accumulated beta-catenin proteins may bind to the lymphocyte enhancer binding factor-1 (LEF-1), form the beta-catenin and LEF -1 complex, and stimulate such promoters regulating the cell cycle as the cyclin D1 gene." + + + +
+ + + +
+ + + + + + 12375019 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Interestingly, both the N- and C-terminal domains of TIEG1 were shown to interact with Lef1 and β-catenin using Duolink assays (Figure xref )." + + + +
+ + + +
+ + + + + + 28201653 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In nuclei, β-catenin associates with the T-cell factor (TCF) and lymphoid enhancer factor (LEF) to induce transcription of target genes xref ." + + + +
+ + + +
+ + + + + + 25170755 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "No binding of LEF-1 or β-catenin was observed at distal (5 kB) upstream sites (data not shown)." + + + +
+ + + +
+ + + + + + 17113388 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The Arm R10-12 sequence facilitated transport even when beta-catenin was bound to the Arm binding partner LEF-1, and its activity was stimulated by phosphorylation at Tyr 654." + + + +
+ + + +
+ + + + + + 22110128 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The Arm R10-12 sequence facilitated transport even when β-catenin was bound to the Arm-binding partner LEF-1, and its activity was stimulated by phosphorylation at Tyr-654." + + + +
+ + + +
+ + + + + + 22110128 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "These results agree with the currently-accepted model that β-catenin associates with DNA-bound LEF1 and functions as a scaffold protein to recruit additional coactivators, such as CARM1 and p300, each of which makes a unique and specific contribution to the highly complex transcriptional initiation process." + + + +
+ + + +
+ + + + + + 21478268 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Mammalian Dpr1 and Dact inhibits expression of Wnt responsive reporters through its promotion of Dvl degradation in a lysosome dependent pathway, and by inhibiting the binding of LEF1 with beta-catenin, but promoting the binding of LEF1 with a corepressor, histone deacetylase 1 (HDAC1) XREF_BIBR, XREF_BIBR." + + + +
+ + + +
+ + + + + + 19440376 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Mammalian Dpr1/Dact inhibits expression of Wnt-responsive reporters through its promotion of Dvl degradation in a lysosome-dependent pathway, and by inhibiting the binding of LEF1 with β-catenin, but promoting the binding of LEF1 with a corepressor, histone deacetylase 1 (HDAC1) xref , xref ." + + + +
+ + + +
+ + + + + + 19440376 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We conclude that residue F660 is essential for ICAT anchoring but plays no role in the β-catenin interaction with LEF1." + + + +
+ + + +
+ + + + + + 28273108 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Additionally, β-catenin interacts with Lef-1 and with Klf4 to activate tert gene transcription." + + + +
+ + + +
+ + + + + + 25262238 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "beta-Catenin is an important partner in LEF1 transcriptional factor activity, and when LEF1 is bound to beta-catenin, LEF1 transports it to the nucleus." + + + +
+ + + +
+ + + + + + 14691138 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "If beta-catenin is bound with LEF1, TGFbeta may not be able to dissociate the complex." + + + +
+ + + +
+ + + + + + 14691138 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In the presence of WNT signals, LEF1 binds to beta-catenin via its N-terminal beta-catenin-binding domain and promotes context dependent target gene transcription including c-MYC and AXIN2." + + + +
+ + + +
+ + + + + + 27965462 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "β-Catenin is an important partner in LEF1 transcriptional factor activity, and when LEF1 is bound to β-catenin, LEF1 transports it to the nucleus ( xref ; xref )." + + + +
+ + + +
+ + + + + + 14691138 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Interaction of LEF1 with nuclear β-catenin is known to effect Wnt signaling by stimulating the activity of LEF1/TCF transcription factors ( xref )." + + + +
+ + + +
+ + + + + + 14691138 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "If β-catenin is bound with LEF1, TGFβ may not be able to dissociate the complex ( xref )." + + + +
+ + + +
+ + + + + + 14691138 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The significance of this was poorly understood until yeast two hybrid studies revealed that the architectural HMG-box transcription factors LEF-1 and XTCF-3 interact with β-catenin ( Behrens et al., 1996; Molenaar et al., 1996 )." + + + +
+ + + +
+ + + + + + 10495268 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In the presence of WNT signals, LEF1 binds to β-catenin via its N-terminal β-catenin-binding domain and promotes context-dependent target gene transcription including c-MYC and AXIN2 ." + + + +
+ + + +
+ + + + + + 27965462 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Since these RMS cell lines express the full-length LEF1 isoform of 44 kDa, whereas the truncated isoform lacking the β-catenin binding site (31 kDa and 23 kDa; see [ xref , xref ]) were barely detected (Figure xref ), we conclude that these cell lines express functional LEF1 that can interact with β-catenin." + + + +
+ + + +
+ + + + + + 27965462 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In some cell types, but not in others, activated beta-catenin interacts with members of the lymphoid enhancer-binding factor (LEF)/T-cell factor (TCF) family of transcription factors and induces gene expression." + + + +
+ + + +
+ + + + + + 11750994 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Nuclear β-catenin associates with the lymphoid enhancer factor/T-cell factor (LEF/TCF) family of transcription factors to induce expression of genes involved in cell proliferation and survival, as well as migration and angiogenesis ( xref , xref )." + + + +
+ + + +
+ + + + + + 25228654 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "XREF_BIBR, XREF_BIBR TGFbeta mediated PI3K-Akt signaling upregulates the transcription factor Snail and induces phosphorylation and inhibition of GSK-3beta which leads to assembly of LEF-1 and beta-Catenin complexes and upregulation of EMT promoting genes." + + + +
+ + + +
+ + + + + + 19471120 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Behrans J, van Kries JP, Kuehl M, Bruhn L, Wedlich +D, o Grosschedl R, Birchmeier W: Functional interaction of beta- +catenin with the transcription factor LEF-1." + + + +
+ + + +
+ + + + + + 9330865 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "As a result, there is cytoplasmic accumulation and nuclear translocation of beta-catenin, where it binds to LEF-1 and TCF, which in turn results in fibronectin induction." + + + +
+ + + +
+ + + + + + 21133803 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Together, the data obtained so far suggested that estradiol might activate a beta-Catenin and LEF -1 complex that is similar to that activated by Wnt in other systems." + + + +
+ + + +
+ + + + + + 19360103 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We observed that association of β-catenin with the LEF-1 promoter was diminished upon FoxM1 depletion ( xref )." + + + +
+ + + +
+ + + + + + 22014570 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Thus, the decreased association of β-catenin with the LEF-1 promoter upon FoxM1 depletion was probably because both the nuclear β-catenin level ( xref ) and the binding between β-catenin and TCF4 were decreased ( xref )." + + + +
+ + + +
+ + + + + + 22014570 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Active beta-catenin is known to translocate to the nucleus and interact with LEF1 to upregulate the expression of canonical target genes." + + + +
+ + + +
+ + + + + + 26473529 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Epistasis analysis suggested that TRABID might act downstream of beta-catenin stabilization and affect the interaction of beta-catenin with LEF1 [ xref ]." + + + +
+ + + +
+ + + + + + 22584113 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "This TFBS was identified by virtue of its interaction with the beta-catenin-T cell-factor/lymphoid-enhancer-factor complex (Tcf/Lef) [ xref ]." + + + +
+ + + +
+ + + + + + 18485226 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "As a result it has been further shown that beta-catenin interacts with the transcription factor LEF1, which is in turn associated with Smad 4, thereby regulating the transcription of TGF-beta target molecules XREF_BIBR." + + + +
+ + + +
+ + + + + + 25036590 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Coimmunoprecipitation data demonstrated that overexpression of NLK protein reduced β-catenin binding to LEF-1." + + + +
+ + + +
+ + + + + + 24395089 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Coimmunoprecipitation data demonstrated that overexpression of NLK protein reduced beta-catenin binding to LEF-1." + + + +
+ + + +
+ + + + + + 24395089 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "As a result it has been further shown that β-catenin interacts with the transcription factor LEF1, which is in turn associated with Smad 4, thereby regulating the transcription of TGF-β target molecules xref ." + + + +
+ + + +
+ + + + + + 25036590 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "While the full-length LEF1, transcribed from upstream promoter, interacts with beta-catenin and regulates Wnt target genes, the shorter isoform is incapable of binding beta-catenin and suppresses the regulation of Wnt targets through beta-catenin." + + + +
+ + + +
+ + + + + + 20843783 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Beta-catenin synthesized in vitro bound strongly and specifically to GST-LEF1 (XREF_FIG C, upper panel), but GAC63 synthesized in vitro did not (XREF_FIG C, lower panel)." + + + +
+ + + +
+ + + + + + 17344318 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Nurr1 was reported to interact with β-catenin and Lef-1 in 293F cells [36] ." + + + +
+ + + +
+ + + + + + 21362399 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "This result indicates that β-catenin and Lef1 associate with chromatin at the Tcf/Lef element within the promoter region." + + + +
+ + + +
+ + + + + + 21689639 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "ChIP experiments demonstrated that β-catenin and Lef1 bind to the enhancer region of the gene." + + + +
+ + + +
+ + + + + + 21689639 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "This regulation required Rac1 dependent phosphorylation of beta-catenin at specific serines, which when mutated (S191A and S605A) reduced beta-catenin binding to LEF-1 by up to 50%, as revealed by PLA and immunoprecipitation experiments." + + + +
+ + + +
+ + + + + + 26403202 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "However, it is also possible that Rac1 stimulates beta-catenin nuclear transactivation function by stabilizing the interaction between beta-catenin and LEF-1 (summarized in XREF_FIG A)." + + + +
+ + + +
+ + + + + + 26403202 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Moreover, treatment with the Rac1 inhibitor NSC23766 resulted in a marked reduction in interactions between beta-catenin and LEF-1 in the nuclei of Wnt treated cells (XREF_FIG B)." + + + +
+ + + +
+ + + + + + 26403202 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "These results, when considered together, suggest that active Rac1 can stimulate complex formation between beta-catenin and LEF-1 and contributes to the positive effect of Wnt on the assembly of beta-catenin-LEF-1 complexes in cells (XREF_FIG B, D)." + + + +
+ + + +
+ + + + + + 26403202 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "To gain further insight into the effect of Rac1 on the interaction between beta-catenin and LEF-1 we analyzed the consequences of mutating the Rac1 sensitive beta-catenin serine residues S191 and S605 on binding of LEF-1." + + + +
+ + + +
+ + + + + + 26403202 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Our findings instead suggest that Rac1 enhances the interaction between beta-catenin and LEF-1, providing a plausible new explanation for the role of Rac1 in augmenting transactivation of Wnt target genes." + + + +
+ + + +
+ + + + + + 26403202 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "We propose that this stimulates binding of beta-catenin to LEF-1, leading to enhanced Wnt signaling responses." + + + +
+ + + +
+ + + + + + 26403202 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Thus further understanding of the mechanism by which Rac1 modulates the interaction between LEF-1 and beta-catenin may provide an alternative therapeutic avenue to reduce beta-catenin-LEF-1 signaling in colorectal cancer." + + + +
+ + + +
+ + + + + + 26403202 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Upon Wnt stimulation, LEF1 or other TCF/LEF family transcription factors associate with beta-catenin, a key cytoplasmic and nuclear mediator of Wnt pathway, and activate Wnt responsive target genes." + + + +
+ + + +
+ + + + + + 21383983 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "β-catenin may increase FoxO transcriptional activity and competitively limit β-catenin interaction with members of the lymphoid enhancer factor/T cell factor family [ xref ] and β-catenin also has been demonstrated to be necessary for protection against amyloid toxicity in neuronal cells [ xref ]." + + + +
+ + + +
+ + + + + + 18554157 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Moreover, binding of Lef1 and beta-catenin to the Lef1 binding site transactivates COX-2 promoter activity." + + + +
+ + + +
+ + + + + + 17945188 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Moreover, binding of Lef1 and beta-catenin to the Lef1-binding site transactivates COX-2 promoter activity." + + + +
+ + + +
+ + + + + + 17945188 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Upon accumulation, β-catenin interacts with members of the lymphoid enhancer factor/T-cell factor (Lef-1/TCF) family to generate a functional transcription factor complex [2,6,7] which in turn induces constitutive transcriptional activation of distinct target genes, e.g. c-myc [8,9] ." + + + +
+ + + +
+ + + + + + 20840866 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "This regulation required Rac1-dependent phosphorylation of β-catenin at specific serines, which when mutated (S191A and S605A) reduced β-catenin binding to LEF-1 by up to 50%, as revealed by PLA and immunoprecipitation experiments." + + + +
+ + + +
+ + + + + + 26403202 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "However, it is also possible that Rac1 stimulates β-catenin nuclear transactivation function by stabilizing the interaction between β-catenin and LEF-1 (summarized in xref A)." + + + +
+ + + +
+ + + + + + 26403202 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Similarly, the transient expression of WT-Rac1 or constitutively active (Q61L)-Rac1 caused a significant increase in nuclear β-catenin–LEF-1 interactions relative to control ( xref B)." + + + +
+ + + +
+ + + + + + 26403202 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Importantly, we were able to show by IP that the Rac1 inhibitor reduced formation of ectopic LEF-1–β-catenin complexes both before and after LiCl treatment ( xref C;–)." + + + +
+ + + +
+ + + + + + 26403202 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "These results, when considered together, suggest that active Rac1 can stimulate complex formation between β-catenin and LEF-1 and contributes to the positive effect of Wnt on the assembly of β-catenin–LEF-1 complexes in cells ( xref B,D)." + + + +
+ + + +
+ + + + + + 26403202 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "To gain further insight into the effect of Rac1 on the interaction between β-catenin and LEF-1 we analyzed the consequences of mutating the Rac1-sensitive β-catenin serine residues S191 and S605 on binding of LEF-1." + + + +
+ + + +
+ + + + + + 26403202 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We next used immunoprecipitation assays to measure binding efficacy between myc-tagged forms of β-catenin and LEF-1, using an anti-HA antibody to pull down ectopic HA-LEF-1." + + + +
+ + + +
+ + + + + + 26403202 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Our findings instead suggest that Rac1 enhances the interaction between β-catenin and LEF-1, providing a plausible new explanation for the role of Rac1 in augmenting transactivation of Wnt target genes." + + + +
+ + + +
+ + + + + + 26403202 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We propose that this stimulates binding of β-catenin to LEF-1, leading to enhanced Wnt signaling responses." + + + +
+ + + +
+ + + + + + 26403202 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Our model ( xref ) details the proposed steps for Rac1 involvement in canonical Wnt signaling: (1) activation (GTP-loading) of Rac1 reduces its association with the plasma membrane and causes active Rac1–β-catenin complexes to dissociate from the membrane, (2) these active Rac1–β-catenin complexes translocate to the cytoplasm and nucleus, (3) active Rac1 mediates the phosphorylation of β-catenin at S191 and S605 via JNK2 kinase in the cytoplasm and possibly the nucleus, and (4) the newly phosphorylated β-catenin preferentially binds to LEF-1 to boost gene transactivation." + + + +
+ + + +
+ + + + + + 26403202 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Chibby and ICAT, two physiological inhibitors of β-catenin–LEF-1 interaction ( xref ; xref ) both bind within this region, whereas LEF-1 binds between S191 and S605 within the arm repeats 3–9 ( xref )." + + + +
+ + + +
+ + + + + + 26403202 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We speculate that addition of the phosphate group at S605 might disturb interaction between β-catenin and the inhibitors, but retains or enhances β-catenin interaction with LEF-1 and recruitment of transcriptional co-activators such as BCL9, pygopus, Mediator and CBP ( xref )." + + + +
+ + + +
+ + + + + + 26403202 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The development of small molecule inhibitors targeting β-catenin–LEF-1 interactions have been met with specificity difficulties due to an overlapping binding region between LEF-1/TCFs and destruction complex members such as APC and Axin ( xref )." + + + +
+ + + +
+ + + + + + 26403202 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Thus further understanding of the mechanism by which Rac1 modulates the interaction between LEF-1 and β-catenin may provide an alternative therapeutic avenue to reduce β-catenin–LEF-1 signaling in colorectal cancer." + + + +
+ + + +
+ + + + + + 26403202 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The thermodynamics of beta-catenin binding to E-cadherin, Lef-1, APC, axin, and the transcriptional inhibitor ICAT have been determined by isothermal titration calorimetry." + + + +
+ + + +
+ + + + + + 16293619 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Nuclear CTNNB1 binds the transcription factors LEF1 (lymphoid enhancer binding factor 1) and TCF (T-cell factor), thereby converting LEF1 into a transcriptional activator." + + + +
+ + + +
+ + + + + + 23442321 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In agreement with these results, several of the new candidates bind to LEF1, and it is well established that TCF and LEF1 forms a complex with beta-catenin to activate the expression of genes under the canonical Wnt pathway [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 20515496 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Being expressed in the nucleus, β-catenin could bind with lymphoid enhancing binding factor-1/T-cell factor-4 (LEF-1/TCF-4) xref , xref ." + + + +
+ + + +
+ + + + + + 26078714 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Beta-catenin and LEF1 complexes formed in the absence of KLF4 (XREF_SUPPLEMENTARY), and, interestingly, TCF4 and KLF4 complex formation was unaffected by beta-catenin deletion (XREF_SUPPLEMENTARY)." + + + +
+ + + +
+ + + + + + 28589954 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Importantly, LEF-1-bound beta-catenin was protected from degradation by APC and axin in SW480 colon cancer cells." + + + +
+ + + +
+ + + + + + 11986304 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Lef-1 and β-catenin form a functional transcription factor complex as a result of Wnt signaling, and their overexpression can bypass a Wnt signal ( Behrens et al., 1996 )." + + + +
+ + + +
+ + + + + + 12039047 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "This could be explained by a likely association of over-expressed Lef-1 protein with endogenous β-catenin." + + + +
+ + + +
+ + + + + + 12039047 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Accumulated β-catenin associates with members of the lymphoid enhancer-binding factor/T-cell factor (LEF/TCF) family to regulate specific target genes such as c-myc, cyclin D1, CD44, and Axin2 xref ." + + + +
+ + + +
+ + + + + + 27668402 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Central regions of Tcf7s and Lef1 interact weakly with β-catenin and strongly with co-repressors, including Hdacs and Tle proteins." + + + +
+ + + +
+ + + + + + 22079544 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Further, while it is known that beta-catenin and LEF1 are transcriptional coactivators and form a complex within the nucleus, and that beta-catenin co-activates LEF1 transcription, these proteins are rarely studied together in context of disease." + + + +
+ + + +
+ + + + + + 27067790 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Furthermore, mammalian Dact1 inhibits the binding of Lef-1 with beta-catenin and promotes the interaction of Lef-1 with histone deacetylase (HDAC1) a co-repressor XREF_BIBR, XREF_BIBR." + + + +
+ + + +
+ + + + + + 23349981 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Dapper1, originally identified as a protein binding to Dishevelled, can associate with HDAC1 and enhance the interaction of Lef1 with HDAC1 (at the expense of Lef1 binding to beta-catenin), thus maintaining Lef1 in the repressive state, as previously proposed." + + + +
+ + + +
+ + + + + + 19433865 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Furthermore, mammalian Dact1 inhibits the binding of Lef-1 with β-catenin and promotes the interaction of Lef-1 with histone deacetylase (HDAC1) a co-repressor xref , xref ." + + + +
+ + + +
+ + + + + + 23349981 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "It was previously shown that Dact2 inhibits Lef-1 interaction with β-catenin, however, Dact2 does not appear to inhibit the interaction of Pitx2 with β-catenin or Lef-1, but modulates their synergistic transcriptional activities." + + + +
+ + + +
+ + + + + + 23349981 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In the nucleus, beta-catenin binds to and activates the TCF/LEF transcription factor complex to induce the expression of wnt-pathway genes, such as, EphB2, EphB3, TCF4 and LEF1." + + + +
+ + + +
+ + + + + + 19956666 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In the nucleus, beta-catenin interacts with the transcription factor LEF-1, which activates transcription of the target genes [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 22229032 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Based on these insights, new therapeutic opportunities have been explored by investigators who show that small-molecule WNT-pathway inhibitors, which inhibit the interaction between β-catenin and LEF1, selectively induce cell death in AML cell lines and primary AML blasts [ xref ]." + + + +
+ + + +
+ + + + + + 27571104 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Based on these insights, new therapeutic opportunities have been explored by investigators who show that small-molecule WNT-pathway inhibitors, which inhibit the interaction between beta-catenin and LEF1, selectively induce cell death in AML cell lines and primary AML blasts [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 27571104 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The chromatin immunoprecipitation assay assay showed beta-catenin and LEF -1 heterodimer could directly bind to the promoter of Mre11 in vivo." + + + +
+ + + +
+ + + + + + 20956948 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Expression of the MYF5 gene is regulated directly by CTNNB1 and LEF1 binding and transcriptional co-activation of the MYF5 epaxial enhancer XREF_BIBR." + + + +
+ + + +
+ + + + + + 28165492 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Subsequently beta-catenin interacts with members of the lymphoid enhancer factor 1/T-cell factor (LEF1/TCF) family, resulting in a functional transcription factor complex and the expression of downstream target genes. xref , xref The non-canonical Wnt ligands also bind to FZD family receptors, and ROR2 and RYK co-receptors. xref - xref The non-canonical signaling pathways include three pathways (Wnt/Ca 2+ , Wnt/G protein, and Wnt/PCP signaling pathways) and non-canonical signaling regulates cell polarity and movement. xref - xref Among the five Wnt antagonist families (secreted frizzled-related protein (sFRP), Wnt inhibitory factor 1 (Wif1), Xenopus Cerberus, Wise and Dickkopf (DKK) families) the DKK family consists of four main members (DKK1-4) which contain two distinct cysteine-rich domains. xref , xref Our lab has studied several Wnt antagonist genes and these function in renal cancer. xref - xref Previously DKK4 has been thought to act as an inhibitor of Wnt/beta-catenin signaling in colorectal cancer. xref , xref Recently two groups found that DKK4 expression was increased in colon cancer tissues compared to matched normal colon tissues and DKK4 was induced by activated beta-catenin, although DKK4 itself significantly inhibited TCF/LEF reporter activity in colon cancer cell lines. xref , xref As far as we know, there have been no reports regarding DKK4 and renal cancer." + + + +
+ + + +
+ + + + + + 21472712 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Wnt signaling induces the stabilization of cytosolic beta-catenin, which then associates with lymphoid enhancer factor and T-cell factor (LEF-1/TCF) to form a transcription complex that activates Wnt target genes." + + + +
+ + + +
+ + + + + + 12556497 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Subsequent transforming growth factor (TGF)-beta3 signaling increases LEF-1 gene expression causing formation of beta-catenin-lymphoid enhancer factor (LEF)-1 complexes that initiate EMT." + + + +
+ + + +
+ + + + + + 18799618 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "It is known that nuclear beta-catenin is able to bind TCF and Lef1 and activate transcription XREF_BIBR, XREF_BIBR." + + + +
+ + + +
+ + + + + + 25003522 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "To determine whether the beta, catenin, LEF1, and TCF complex might directly regulate Cacna1g, Cacna2d2, Kcna6, Kcnh8, Drd3, Gabra3, Glra1, Grid2, and Calb2, we analyzed the in vivo binding of beta-catenin to LEF1 and TCF motifs within the CNSs using a chromatin immunoprecipitation (ChIP) assay with designed primers." + + + +
+ + + +
+ + + + + + 23157480 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Here, the stable β-catenin interacts with the lymphoid enhancer factor/T cell factor (LEF/TCF) and is translocated into the nucleus as a complex of β-catenin/LEF/TCF to stimulate target gene transcription by displacement of groucho-HDAC co-repressors xref , xref ." + + + +
+ + + +
+ + + + + + 23490077 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Beta-catenin and LEF1 signaling is activated in CLL cells, and inhibition of beta-catenin and LEF1 interaction has been proved to induce apoptosis in CLL cells [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 26950276 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "However, our results also demonstrate that a complete loss of E-cadherin and transformation to the mesenchymal phenotype are dependent on Smad signaling, which subsequently stimulates formation of beta-catenin and LEF -1 complexes that induce EMT." + + + +
+ + + +
+ + + + + + 16467384 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The mutations impaired both LEF1 binding to beta-catenin and transcriptional activation, and are the first tumor-associated mutations that inactivate Wnt signaling." + + + +
+ + + +
+ + + + + + 16565724 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "As transcriptional activity of Lef1 is controlled by recruitment of its co-activator β-catenin, we tested whether Lef1 and β-catenin can form a ternary complex on the TCF/LEF site ( xref F and 5G)." + + + +
+ + + +
+ + + + + + 26212321 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The mutations impaired both LEF1 binding to beta-catenin and transcriptional activation, and are the first tumor associated mutations that inactivate Wnt signaling." + + + +
+ + + +
+ + + + + + 16565724 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The same is true for mammalian cells, where FHL2 does not interfere with the β-catenin–LEF-1 interaction (unpublished data)." + + + +
+ + + +
+ + + + + + 12370240 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "This TNKSi insensitivity is conferred by β-catenin’s association with LEF1 and BCL9-2/B9L, which accumulate during Wnt stimulation, thereby providing a feed-forward loop that converts transient into chronic β-catenin signaling." + + + +
+ + + +
+ + + + + + 24419084 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Intratumoral, peritumoral and Crohn’s-like lymphoid reactions were not significantly associated with nuclear CTNNB1 expression ( P > 0.14)." + + + +
+ + + +
+ + + + + + 29510987 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In the nucleus, β-catenin associates with the lymphoid enhancer factor/T-cell factor (LEF/TCF) family of transcription factors, converting them from transcription repressors to activators, thereby activating a wide range of Wnt responsive genes xref – xref ." + + + +
+ + + +
+ + + + + + 31273221 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "This correlated with upregulation of LEF1, a nuclear binding partner of beta-Catenin." + + + +
+ + + +
+ + + + + + 31463973 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Both, complete LEF1-deficiency and prevention of the β-Catenin-LEF1 interaction impaired the ability of SNAIL1 to elicit expression of an alternative set of Wnt/β-catenin targets, and to promote cancer cell invasion." + + + +
+ + + +
+ + + + + + 31463973 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "To directly assay for binding of LEF-1 and beta-catenin to these sites, electrophoretic gel-mobility shift analysis was performed with recombinant LEF-1 and beta-catenin produced in E. coli." + + + +
+ + + +
+ + + + + + 10704849 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "These experiments show that there is specific binding of the beta-catenin and LEF -1 complex to either or both of the two TCF recognition sites in the Brachyury promoter." + + + +
+ + + +
+ + + + + + 10704849 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Similarly, the interaction between nuclear beta-catenin and TCF-4 or LEF-1 was reduced by CaSR activation, indicating an inhibitory association of beta-catenin and TCF-4 or LEF-1 in the nucleus." + + + +
+ + + +
+ + + + + + 27108064 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "LEF-1 and beta-catenin form a complex that regulates promoter activation in concert with PAX-5 in immature B cells (Jin et al., 2002)." + + + +
+ + + +
+ + + + + + 21184762 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Because LEF-1 possesses its own NLS (Huber et al., 1996) and is able to interact with beta-catenin, we asked whether glucose favored LEF-1 and beta-catenin interaction as a possible mechanism for the nuclear accumulation of beta-catenin." + + + +
+ + + +
+ + + + + + 23273980 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Thus, the availability of LEF-1 may be critical for LEF-1 and beta-catenin interaction and nuclear accumulation.Given that acetylation of beta-catenin through p300 or CBP (Wolf et al., 2002; Xu and Kimelman, 2007) and its deacetylation by SIRT1 (Firestein et al., 2008) impacts its oncogenicity, we examined whether combined LiCl and glucose treatment altered the levels of the acetylase p300 and the deacetylase SIRT1." + + + +
+ + + +
+ + + + + + 23273980 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Collectively, the results indicate that combined glucose and LiCl treatment increases p300-LEF-1-beta-catenin interaction while preventing SIRT1-LEF-1 and SIRT1-beta-catenin interaction and suggest that increased acetylation by p300 may be required for nuclear retention of the LEF-1 and beta-catenin complex.Endogenous beta-catenin underwent nuclear accumulation following glucose and LiCl stimulation; by contrast, a beta catenin mutant unable to interact with LEF-1 (Delta19 beta-catenin) (Orsulic and Peifer, 1996; Prieve and Waterman, 1999) was unable to accumulate in the nucleus, suggesting that beta-catenin and LEF -1 interaction was required for nuclear retention.The requirement of LEF-1 for mediating the p300 and beta-catenin interaction was examined in a western blot for p300 on anti-myc immunoprecipitates from cells transfected with Myc tagged wild-type (WT) or Delta19beta catenin mutant and treated with LiCl, glucose, both, or none." + + + +
+ + + +
+ + + + + + 23273980 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Whereas ectoptic WT beta-catenin bound p300 upon exposure of the cells to both glucose and LiCl (like endogenous beta-catenin), conditions that promote LEF-1 and beta-catenin interaction and nuclear accumulation of beta-catenin, the Delta19 beta catenin mutant was unable to bind p300 under any conditions." + + + +
+ + + +
+ + + + + + 23273980 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Given that p300 binds the C terminus of beta-catenin (Hecht et al., 2000) more than 300 amino acids away from the region missing in Delta19 beta-catenin (arms 5-6), our results suggest that LEF-1 and beta-catenin complexes recruit p300 more efficiently than does beta-catenin alone." + + + +
+ + + +
+ + + + + + 23273980 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Thus, the LEF-1 and beta-catenin interaction promoted by the combination of glucose and LiCl appears critical for stabilizing p300 interaction and nuclear retention.To test whether beta-catenin acetylation is increased under the conditions required for nuclear accumulation, we immunoprecipitated nuclear extracts with acetyllysine antibody and detected beta-catenin or immunoprecipitated with anti-beta-catenin and detected anti-acetyllysine." + + + +
+ + + +
+ + + + + + 23273980 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Although the precise molecular mechanisms have not been explored here, we view it as probable that SIRT1 acts as a competitor for interaction between LEF-1 and beta-catenin." + + + +
+ + + +
+ + + + + + 23273980 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Treatment with lithium chloride, microinjection of constitutive beta-catenin, HDAC1 IgG, or the addition of serum all acted to reverse this repressive function.Immunoprecipitation from cells transfected with a Pitx2 expression vector revealed the ability of Pitx2 to robustly interact with beta-catenin and with HDAC1, even at endogenous levels of Pitx2 and beta-catenin, analogous to interactions between TCF and LEF1 and beta-catenin." + + + +
+ + + +
+ + + + + + 12464179 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "This data implicates a strong association between beta-catenin and LEF-1 within the nuclei of cells, as confirmed by immunoprecipitation assay with the nuclear chromatin fraction of MCF-7 cells." + + + +
+ + + +
+ + + + + + 26844628 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "How does the binding of beta-catenin to LEF-1 and TCF proteins affect cooperative interactions at a promoter or enhancer?" + + + +
+ + + +
+ + + + + + 10209158 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "LiCl activation of the Wnt and beta-catenin signaling pathway causes nuclear accumulation of beta-catenin, which binds with TCF and LEF1 transcription factor to modulate the expression of downstream genes such as C-myc and cyclin D1 that regulate the cell cycle and growth (Kanei-Ishii et al., 2004)." + + + +
+ + + +
+ + + + + + 29679546 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In human osteoblasts, a naturally occurring LEF1 isoform lacking the N-terminus can still associate with beta-catenin and activate Wnt targets (Hoeppner et al." + + + +
+ + + +
+ + + + + + 22305157 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In addition, an antisense DeltaNp63alpha construct (DeltaNp63alpha-AS) reduced luciferase activity mediated by the endogenous beta-catenin and Lef -1 complex, while TAp63alpha had no effect on this activity." + + + +
+ + + +
+ + + + + + 12086851 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In the nucleus beta-catenin binds to Lef1 and TCF transcription factors to initiate gene activation.The importance of Wnt signaling in bone development became obvious following the discovery of gain- and loss-of-function mutations of human LRP5." + + + +
+ + + +
+ + + + + + 19389391 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Further, Shtutman and colleagues 83 demonstrated that the beta-catenin and LEF -1 complex binds to the cyclin D1 promoter, and the promotion of cyclin D1 expression by beta-catenin is inhibited by transfection with wild-type APC and/or AXIN." + + + +
+ + + +
+ + + + + + 11839557 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "93 The changes in COX-2 described in the latter study model are also associated with increased beta-catenin and LEF -1 complex formation." + + + +
+ + + +
+ + + + + + 11839557 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "LEF-1 and TCF proteins associate with beta-catenin through amino-terminal sequences, and together these proteins mediate a transcriptional response to Wnt signaling.Wnt proteins represent a growing family of secreted signaling molecules that are expressed in diverse tissues and have been shown to influence multiple processes in vertebrate and invertebrate development (reviewed in Cadigan and Nusse 1997)." + + + +
+ + + +
+ + + + + + 10933391 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "LEF1, in turn, binds to the promoter regions of at least two direct target genes (Lmx1a and Fgf20) and together with beta-catenin appears to activate their transcription in the mutant VM." + + + +
+ + + +
+ + + + + + 26049140 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "However, in-depth study is needed to investigate the mechanisms regulating GSK3beta activity in PDLSCs under inflammatory conditions.Our findings demonstrated that in the inflammatory microenvironments, TNF-alpha induced the phosphorylation of GSK3beta, and the p-GSK3beta subsequently resulted in nuclear beta-catenin accumulation and beta-catenin and Lef -1 complex formation, which inhibited Runx2 associated the osteogenesis of PDLSCs." + + + +
+ + + +
+ + + + + + 23911749 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "29 These inhibitors and their mechanism of action (inhibition of LEF-1 and beta-catenin binding) are being more fully explored with the development of a LEF-1 and beta-catenin FRET assay." + + + +
+ + + +
+ + + + + + 12659745 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In pull-down assays, HINT1 did not bind to beta-catenin or LEF-1 nor did it impair the LEF-1 and beta-catenin interaction or the binding of pontin or reptin to beta-catenin." + + + +
+ + + +
+ + + + + + 21316334 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "This increases the pool of cytoplasmic beta-Catenin, which translocates to the nucleus and then binds with LEF-1 to modulate transcription of target genes.A role for the TGF-beta pathway in desmoid cells can be hypothesized based on its central role in fibroblastic proliferation." + + + +
+ + + +
+ + + + + + 17601559 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "T246M) mutant does not affect the interaction, while knockdown of CHIP decreases the endogenous interaction of LEF1-β-catenin complex." + + + +
+ + + +
+ + + + + + 33431799 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Moreover, the miR-371-373 cluster is activated by Wnt signaling through the direct binding of beta-catenin and LEF1 to the promoter region and then forms a positive feedback loop with Wnt signaling by repressing DKK1 [25]." + + + +
+ + + +
+ + + + + + 26255203 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Functional interaction of beta- catenin with the transcription factor LEF-1." + + + +
+ + + +
+ + + + + + 10503270 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The nuclear beta-catenin interacts with the transcription factor LEF1 to activate target gene expression (Behrens et al., 1996; Hsu et al., 1998)." + + + +
+ + + +
+ + + + + + 16890162 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "These results suggest that Tob1a inhibits the interaction between beta-catenin and LEF1 solely by competing with LEF1 for beta-catenin." + + + +
+ + + +
+ + + + + + 16890162 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Thus, expression of the OSTM1DeltaC mutant blocked the ability of Wnt3a to signal to a major embryonic response, PE formation.The epistasis experiments implicated OSTM1DeltaC action on Wnt and beta-catenin signaling, downstream of beta-catenin accumulation, but upstream of beta-catenin and Lef1 interaction." + + + +
+ + + +
+ + + + + + 18296023 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "We compared the ability of OSTM1 and OSTM1DeltaC to regulate the Wnt3a induced binding of beta-catenin to Lef1." + + + +
+ + + +
+ + + + + + 18296023 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Beta-catenin binding to Lef1 increased in cells treated with Wnt3a." + + + +
+ + + +
+ + + + + + 18296023 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Furthermore, we determined the mechanism whereby OSTM1 regulates Wnt signaling : through modulation of the beta-catenin and Lef1 interaction, a crucial downstream event in Wnt and beta-catenin signal transduction.In order to assess the effect of OSTM1 overexpression or suppression on Wnt and beta-catenin signaling we utilized a luciferase based Lef and Tcf sensitive reporter construct which can be activated in response to Wnt3a or transfection with constitutively active Wnt signaling components [21]." + + + +
+ + + +
+ + + + + + 18296023 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Therefore, we tested the ability of OSTM1 and OSTM1DeltaC to regulate the beta-catenin and Lef1 interaction." + + + +
+ + + +
+ + + + + + 18296023 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "It will be informative to probe the beta-catenin and Lef1 interaction in cells from grey-lethal mice or ARO patients with OSTM1 deficiency.Finally, expression of OSTM1DeltaC was shown to inhibit the formation of primitive endoderm in response to Wnt3a." + + + +
+ + + +
+ + + + + + 18296023 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Quantitative analysis indicated that SPDEF disrupted the binding between beta-catenin and TCF1 or TCF3, but did not affect the binding between beta-catenin and LEF1 or TCF4." + + + +
+ + + +
+ + + + + + 28390865 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Stimulation of mutated Wnt and beta-catenin pathway is well recognized as an early stage in colon carcinogenesis that eventually leads to transcription of beta-catenin and LEF -1 complex such as c-Myc and cyclin-D1 [60]." + + + +
+ + + +
+ + + + + + 26482805 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Similar mutations, leading to an increased half-life of beta-catenin, were identified in several human melanoma cell lines leading to a constitutively active beta-catenin and Lef -1 complex in these cells [91]." + + + +
+ + + +
+ + + + + + 10528152 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The significance of this was poorly understood until yeast two hybrid studies revealed that the architectural HMG-box transcription factors LEF-1 and XTCF-3 interact with beta-catenin (Behrens et al., 1996; Molenaar et al., 1996)." + + + +
+ + + +
+ + + + + + 10495268 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Upon accumulation, beta-catenin interacts with Lef-1 and Tcfs to generate a functional transcription factor complex (Behrens et al. 1996; van de Wetering et al. 1997)." + + + +
+ + + +
+ + + + + + 9845363 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In addition, we found evidence that this effect is mediated by Cdx-1 in cells that give rise to the cervical vertebrae.Previous studies have found that cdx-1 expression is stimulated by Wnt signaling through Tcf binding sites in cultured cells, and further that LEF1 and beta-catenin complexes bind to a cdx-1 promoter fragment directly in vitro (Lickert et al., 2000; and M.I. and S.T., unpublished data)." + + + +
+ + + +
+ + + + + + 11335109 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "She found that the HMG box protein TCF-1 and Lef-1 can associate with beta -catenin, and can bind to target DNA as a complex [16]." + + + +
+ + + +
+ + + + + + 9061012 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Elevated beta-catenin levels in colorectal cancer caused by mutations in either beta-catenin or in the adenomatous polyposis coli protein, which regulates the degradation of beta-catenin, result in the increased formation of transcriptionally active beta-catenin and LEF -1 complexes [82,83]." + + + +
+ + + +
+ + + + + + 11223032 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In both Xenopus and Drosophila, LEF-1 and TCF-1-like proteins bind beta-catenin and appear to translocate with it to the nucleus (Behrens et al. 1996; Riese et al. 1997; van de Wetering et al. 1997)." + + + +
+ + + +
+ + + + + + 9288749 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Additionally, beta-catenin interacts with Lef-1 and with Klf4 to activate tert gene transcription." + + + +
+ + + +
+ + + + + + 25262238 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "These data suggest that Lef1 requires the HMG domain to activate the Col11a1 promoter, either through its DNA binding domain or through interaction with other proteins.In many systems, Lef1 interaction with beta-catenin is necessary for Lef1 mediated activation of target genes (reviewed in Behrens et al. 1996; Clevers and van de Wetering, 1997)." + + + +
+ + + +
+ + + + + + 18280717 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Behrens, J. et al. (1996) Functional interaction of beta-catenin with the transcription factor LEF-1." + + + +
+ + + +
+ + + + + + 27568239 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "During gastrulation, β-catenin forms a complex with LEF-1 to bind and inhibit the transcription of CDH1 and induce EMT [ xref ]." + + + +
+ + + +
+ + + + + + 32334405 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "During gastrulation, beta-catenin forms a complex with LEF-1 to bind and inhibit the transcription of CDH1 and induce EMT [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 32334405 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In particular, the increased Histone Deacetylase 6 (HDAC6) expression induces the activation of the nuclear β-catenin-lymphoid enhancer binding factor 1 (LEF1)/T-cell factor-4 (TCF4) transcriptional complex and, in turn, that of the oncogene c-Myc [ xref ]." + + + +
+ + + +
+ + + + + + 32764471 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Cell (Cambridge, Mass.) 111, 251–263 *Behrens, J., von Kries, J.P., Kuhl, M., Bruhn, L., Wedlich, D., Grosschedl, R. and Birchmeier, W. (1996) Functional interaction of β-catenin with the transcription factor LEF-1." + + + +
+ + + +
+ + + + + + 15715524 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Behrens J, von Kries JP, Kuhl M, Bruhn L, Wedlich D, Grosschedl R, Birchmeier W. Functional interaction of beta-catenin with the transcription factor LEF1." + + + +
+ + + +
+ + + + + + 25914082 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Ets gene PEA3 cooperates with beta-catenin-Lef-1 and c-Jun in regulation of osteopontin transcription." + + + +
+ + + +
+ + + + + + 18343725 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Functional interaction of beta-catenin with the transcription factor LEF-1." + + + +
+ + + +
+ + + + + + 22716317 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Cell 119, 641–651 +Behrens, J., von Kries, J. P., Kuhl, M., Bruhn, L., Wedlich, D., Grosschedl, R. and Birchmeier, W. (1996) Functional interaction of beta-catenin with the transcription factor LEF-1." + + + +
+ + + +
+ + + + + + 18823282 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Here, β-catenin interacts with members of the lymphoid enhancer-binding factor (LEF)1/T-cell factor (TCF) transcription factor family and is translocated into the nucleus to stimulate transcription of a wide range of target genes, such as myc and cyclin D1, which are important regulators of epithelial cell proliferation [37,38]." + + + +
+ + + +
+ + + + + + 30743809 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Behrens J, von Kries JP, Ku¨ hl M, Bruhn L, Wedlich D, Grosschedl R et al. Functional interaction of beta-catenin with the transcription factor LEF-1." + + + +
+ + + +
+ + + + + + 22716317 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Of note, β-catenin binds to Lef1 and activates Lef1 transcription complex, leading to down-regulation of E -cadherin expression [ xref ]." + + + +
+ + + +
+ + + + + + 33388549 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Additionally, inhibiting the binding of LEF1 to beta-catenin impaired AML growth, in contrast to spared normal hematopoietic stem cells [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 32872365 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The transient or stable expression of Wnt1 could induce the formation of β-catenin–LEF1 complex and the persistent activation of canonical Wnt signaling in CRC cells ( xref )." + + + +
+ + + +
+ + + + + + 32923386 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In the nucleus, β-catenin binds and activates the lymphoid enhancer factor (LEF)/T cell factor (TCF) transcription factor to regulate the expression of Wnt target genes ( xref )." + + + +
+ + + +
+ + + + + + 33071819 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Behrens J, Von Kries JP, Kuhl M, Bruhn L, Wedlich D, Grosschedl R, et al. Functional interaction of β-catenin with the transcription factor LEF-1." + + + +
+ + + +
+ + + + + + 12975039 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Functional interaction of beta-catenin with the transcription factor LEF-1." + + + +
+ + + +
+ + + + + + 12975039 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Rac1 also enhances the nuclear formation of the β-catenin and LEF-1 complexes, providing the basis for the role of Rac1 in augmenting transactivation of Wnt target genes [ xref ]." + + + +
+ + + +
+ + + + + + 32178475 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The interactions between β-catenin and LEF1 have been historically viewed as inseparable." + + + +
+ + + +
+ + + + + + 32824435 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Binding of WNT ligands to their receptor stabilizes β-catenin (encoded by CTNNB1 ), which binds to the transcription factors of the lymphoid enhancer-binding factor (LEF) transcription factor (TCF) family." + + + +
+ + + +
+ + + + + + 21472002 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Optimizations of a novel fluorescence polarization based high-throughput screening assay for beta-catenin and LEF1 interaction inhibitors." + + + +
+ + + +
+ + + + + + 32956692 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "It is accomplished by transactivating MMP-13 promoter activity through LEF1 and beta-catenin binding to the LEF1 binding site in the 3 ' region of the MMP-13 genomic locus." + + + +
+ + + +
+ + + + + + 33572320 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Moreover, beta-catenin and LEF1 interaction regulates beta-catenin nuclear transport as well as the transcriptions of the key oncogenes in Wnt and beta-catenin signaling pathway." + + + +
+ + + +
+ + + + + + 32956692 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "To date, no economical and rapid high-throughput screening (HTS) assay has been reported for the discovery of beta-catenin and LEF1 interaction inhibitors." + + + +
+ + + +
+ + + + + + 32956692 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In this study, we developed a novel fluorescence polarization (FP)-based HTS assay to identify beta-catenin and LEF1 interaction inhibitors." + + + +
+ + + +
+ + + + + + 32956692 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "GST pull-down and surface plasmon resonance (SPR) assay demonstrated that beta-catenin and LEF1 interaction is a potential anticancer target of sanguinarine in vitro." + + + +
+ + + +
+ + + + + + 32956692 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "This newly developed FP screening assay will be vital for the rapid discovery of novel Wnt inhibitors targeting beta-catenin and LEF1 interaction." + + + +
+ + + +
+ + + + + + 32956692 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "As expected, treatment with Wnt3A or EGF increased the binding of β-catenin to LEF-1 ( xref ), and depletion of LEF-1 ( xref ) reduced Wnt3A- or EGF-induced luciferase activity ( xref )." + + + +
+ + + +
+ + + + + + 32860047 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Prompted by these findings, we investigated whether TG2 could affect the interaction of β-catenin with LEF1, inside the nucleus, necessary to induce Wnt genes expression." + + + +
+ + + +
+ + + + + + 33674551 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Elevated levels of DVL3 have also been reported in nonsmall cell lung carcinoma. xref CSNK2A2 (overexpressed 11-fold) is a highly conserved and ubiquitous serine/threonine kinase, over-expressed in many tumors including prostate. xref Cytoplasmic CSNK2A2 opposes the inhibitory role of GSK3B by phosphorylating and activating DVL and β-catenin, while nuclear CSNK2A2 enhances β-catenin:LEF1 transactivation of Wnt target genes. xref Its nuclear localization was previously reported as a poor prognostic indicator in prostate cancer, xref potentially through its promotion of AR-dependent transcription. xref Downstream component of the pathway, transcription factor LEF1 was also significantly over-expressed and has recently shown to promote AR expression and consequently enhance growth and invasion ability of prostate cancer cells in vitro . xref " + + + +
+ + + +
+ + + + + + 22915211 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Nuclear β-catenin binds to and activates T cell factor (TCF) and lymphoid enhancer-binding (LEF) TFs, which directly bind to specific DNA sequences, enhancing the transcription of genes such as Cyclin D, c-Myc, and Axin2 and inhibiting transcription of other genes such as E-cadherin and the tumor suppressor p53 [ xref , xref ]." + + + +
+ + + +
+ + + + + + 33668092 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Considering the specific expression of Lef1 in the RG cells and not in the IPCs, the induction of β-catenin expression should form heterodimeric activators with Lef1 in the RG cells and lead to downstream target activation and generation of IPCs from the RG cells." + + + +
+ + + +
+ + + + + + 23257686 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Examination of individual NC genes confirmed the association of LEF1 and CTNNB1 with tissue-specific enhancers." + + + +
+ + + +
+ + + + + + 33852891 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We selected 30 genomic regions that interact with promoters of NC genes and are associated with both LEF1 and CTNNB1." + + + +
+ + + +
+ + + + + + 33852891 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "To define the regulatory features of Wnt-associated elements, we examined how LEF1 and CTNNB1 interact with Axud1E1 , an enhancer directly activated by canonical Wnts ( xref )." + + + +
+ + + +
+ + + + + + 33852891 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In our CUT&RUN datasets, approximately 37% of LEF1 binding and 43% of the LEF1/CTNNB1 binding takes place in cis-regulatory regions that only have suboptimal TCF/LEF motifs." + + + +
+ + + +
+ + + + + + 33852891 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "These results are consistent with a scenario in which the loss of Wnt activity in migratory cells drives the dissolution of the LEF1/CTNNB1 complex, leading to the subsequent silencing of the specification GRN." + + + +
+ + + +
+ + + + + + 33852891 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Lef1, a nuclear mediator of Wnt signaling, associates with beta-catenin and activates Wnt responsive genes." + + + +
+ + + +
+ + + + + + 33329029 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In addition, recent data demonstrates that at the onset of anagen, HG exchanging Tcf3/Tcf4 for Lef1 at the super-enhancers, and then Lef1 forms the nuclear complex with β-catenin after activation of WNT signaling (as a consequence of BMP inhibition) which drives HG committed progenitors ( xref ; xref ; xref )." + + + +
+ + + +
+ + + + + + 33363148 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Lymphoid enhancer-binding factor 1 (Lef-1) and β-catenin bind the Pitx2 gene promotor in mice, indicating a role for the canonical Wnt signaling pathway in regulating Pitx2 expression." + + + +
+ + + +
+ + + + + + 33425902 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Of note, beta-catenin binds to Lef1 and activates Lef1 transcription complex, leading to down-regulation of E-cadherin expression [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 33388549 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We can see this demonstrated using synthetic peptide BLBD, which can bind to β-catenin and LEF-1 sites, which results in the decreased formation of breast cancer cells [ xref ]." + + + +
+ + + +
+ + + + + + | PMC + + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We show that overexpression of CHIP promoted the activation of Wnt signaling, and enhanced the interaction between LEF1 and β-catenin through heightening the K63-linked polyubiquitin chains attached to LEF1, while the knockdown of CHIP had the opposite effect." + + + +
+ + + +
+ + + + + + 33431799 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Overexpression of CHIP increased the activation of Wnt signaling, and promoted β-catenin nucleus accumulation by enhancing the interaction between LEF1 and β-catenin through heightening the K63-linked ubiquitination of LEF1." + + + +
+ + + +
+ + + + + + 33431799 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "As shown in Fig. xref , CHIP enhanced the interaction between β-catenin and LEF1, and the interaction was further heightened after Wnt3a treatment, while knockdown of CHIP decreased the interaction (Fig. xref )." + + + +
+ + + +
+ + + + + + 33431799 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Moreover, overexpression of CHIP T246M mutant couldn’t affect the interaction of β-catenin-LEF1 complex (Fig. xref )." + + + +
+ + + +
+ + + + + + 33431799 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "To illuminate whether the heightened interaction of β-catenin and LEF1 was owing to the function of Wnt3a treatment in Fig. xref , we detected the interaction between β-catenin and LEF1 as shown in Fig. xref ." + + + +
+ + + +
+ + + + + + 33431799 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Under Wnt3a stimulation, the interaction between β-catenin and LEF1 was enhanced, and the interaction was more strengthened with the presence of CHIP." + + + +
+ + + +
+ + + + + + 33431799 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We further found CHIP increased the endogenous interaction between β-catenin and LEF1, while CHIP T246M hardly influenced the interaction (Fig. xref )." + + + +
+ + + +
+ + + + + + 33431799 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Knockdown of CHIP reduced the endogenous interaction between β-catenin and LEF1 (Fig. xref )." + + + +
+ + + +
+ + + + + + 33431799 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "These data suggested that CHIP enhanced the interaction between β-catenin and LEF1, and the interaction was further heightened with Wnt3a treatment." + + + +
+ + + +
+ + + + + + 33431799 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "It was in consistent with the enhanced interaction between β-catenin and LEF1 after Wnt3a treatment." + + + +
+ + + +
+ + + + + + 33431799 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Moreover, we verify that CHIP promotes the endogenous interaction between LEF1 and β-catenin, the CHIP (p." + + + +
+ + + +
+ + + + + + 33431799 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Taken together, these results indicate that CHIP accelerates β-catenin nucleus accumulation by promoting interaction between LEF1 and β-catenin through heightening the K63-linked ubiquitination of LEF1." + + + +
+ + + +
+ + + + + + 33431799 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "AEG-1 forms a complex with LEF1 and β-catenin, and AEG-1-mediated activation of the Wnt/β-catenin pathway facilitated the maintenance of glioma stem-like cells and their self-renewal [ xref ]." + + + +
+ + + +
+ + + + + + | PMC + + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Intracellular signal transduction results in the stabilization and nuclear localization of β-catenin, which forms a complex with T cell transcription factors (TCFs) or lymphoid enhancer binding factor 1 (LEF1) to regulate the transcription of target genes [ xref ]." + + + +
+ + + +
+ + + + + + | PMC + + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The nuclear β-catenin could then specifically bind to lymphoid enhancer factor-1 (LEF-1) transcription factors to activate FUT8 transcription." + + + +
+ + + +
+ + + + + + 30619732 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "β-catenin is associated with the lymphoid enhancer factor/T-cell factor family (TCF), converting them from transcription repressors to activators, thereby activating several Wnt-responsive genes ( xref – xref )." + + + +
+ + + +
+ + + + + + 33574925 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In normal epithelial cells, the inhibitory effect of E-cadherin against tumorigenesis is maintained by sequestering the binding of β-catenin to lymphoid enhancer factor (LEF)/T cell factor (TCF); this process could impede the transcription of genes involved in the proliferation-associated Wnt signaling pathway xref ." + + + +
+ + + +
+ + + + + + 33531990 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "And the depletion of FOXG1 diminished the binding of β-catenin to the LEF-1 promoter (Fig. xref e)." + + + +
+ + + +
+ + + + + + 31771611 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In the nucleus, beta-catenin directly interacts with LEF-1, activates the keratin gene, promotes hair growth and regulates the HF cycle." + + + +
+ + + +
+ + + + + + 33393222 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Disassembly of the destruction complex can block β-catenin degradation that results in the translocation of the accumulated β-catenin into the nucleus, where β-catenin binds to the lymphoid enhancer factor/T-cell factor (LEF/TCF) family of transcription factors and triggers the protooncogene-induced transcription of several target genes, such as c-myc, MDR1, OCT4, and cyclin D1 (refs. xref – xref )." + + + +
+ + + +
+ + + + + + 33723262 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Intracellular signal transduction results in the stabilization and nuclear localization of β-catenin, which forms a complex with T cell transcription factors (TCFs) or lymphoid enhancer binding factor 1 (LEF1) to regulate the transcription of target genes [8]." + + + +
+ + + +
+ + + + + + | PMC + + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Another study showed that SP5 and SP8 both assist the binding of β-catenin to LEF1 upon Wnt activation." + + + +
+ + + +
+ + + + + + 34552611 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "We demonstrated that LEF1 and β-catenin bind to and regulate MIR17HG promoter activity, and that activation of the Wnt/β-catenin pathway increases the MIR17HG promoter activity as well as the endogenous expression of miR-17-92 cluster, whereas inactivation of the Wnt/β-catenin pathway reduces miR-17-92 cluster expression." + + + +
+ + + +
+ + + + + + 31191623 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Taken together, all these data suggest that LEF1 and β-catenin specifically bind to and regulate the MIR17HG promoter." + + + +
+ + + +
+ + + + + + 31191623 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "To validate whether LEF1 and β-catenin interact to regulate MIR17HG, we determined the effect of LEF1 and β-catenin interaction on MIR17HG promoter activity." + + + +
+ + + +
+ + + + + + 31191623 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Our results showed that LEF1 and β-catenin could bind to and regulate the MIR17HG promoter (Figure 2)." + + + +
+ + + +
+ + + + + + 31191623 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "And SNAIL affects the EMT process of CRC through various mechanisms such as β-Catenin-LEF1 complexes [ xref ]." + + + +
+ + + +
+ + + + + + | PMC + + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In the nucleus, CTNNB1 forms a complex with LEF1, inhibits the transcriptional activity of E-cadherin, and induces epithelial-mesenchymal transition [23]." + + + +
+ + + +
+ + + + + + 31511060 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "SOX9 has been shown to interact with β-catenin [ xref ], which in turn binds to LEF1 [ xref ]." + + + +
+ + + +
+ + + + + + 35191090 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "SOX9 physically interacts with β-catenin [ xref ], which in turn binds to LEF1 [ xref ]." + + + +
+ + + +
+ + + + + + 35191090 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "By qPCR analysis, RUNX2, ALP, and SPARC, which are associated with osteogenic differentiation, were significantly increased 2.47 ± 0.73-fold ( p  = 0.011), 2.57 ± 0.09-fold ( p  = 0.004), and 2.13 ± 0.60-fold ( p  = 0.018), respectively; LEF1 and β-catenin, which are associated with the Wnt/β-catenin pathway, were increased 1.89 ± 0.45-fold ( p  = 0.012) and 2.22 ± 0.51-fold ( p  = 0.017), respectively (Fig.  xref a)." + + + +
+ + + +
+ + + + + + 31753039 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Further, a more recent study suggests that Wnt-mediated Rac1 activation not only induces nuclear translocation, but also enhances β-catenin and LEF-1 binding in the nucleus ( xref )." + + + +
+ + + +
+ + + + + + 36248967 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In the absence of E-cadherin, there was more interaction between β-catenin and LEF-1 than in E-cadherin wild-type cells." + + + +
+ + + +
+ + + + + + 36248967 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "EpICD directly interacts with beta-catenin and lymphoid enhancer factor (LEF) [ xref ]." + + + +
+ + + +
+ + + + + + 31547062 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "However, this increase in NRARP:LEF1 interactions only translated into increased Wnt signaling activity in Loucy cells as determined by the increase in LEF1:β-catenin interactions in these cells upon NRARP overexpression (Fig. xref g and Supplementary Fig. xref , xref )." + + + +
+ + + +
+ + + + + + 31586130 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In addition, our data shows that NRARP overexpression increases the number of NRARP:LEF1 interactions which in T-ALL cells with low levels of NICD1 translates into more LEF1:β-catenin interactions." + + + +
+ + + +
+ + + + + + 31586130 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Inside the nucleus, β-catenin interacts with T cell transcription factor (TCF) and lymphoid enhancer factor (LEF) and induces transcription of β-catenin target genes [ xref ]." + + + +
+ + + +
+ + + + + + 33049989 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Nuclear DACT2 disrupts the interaction between β-catenin and LEF1, and cytoplasmic DACT2 represses β-catenin nuclear transport via restoring E-cadherin–β-catenin complex [ xref ]." + + + +
+ + + +
+ + + + + + 32961708 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In the nucleus, β-catenin binds to the lymphoid enhancer factor/T-cell factor to initiate the transcription of target genes that promote the proliferation, migration, and invasion of cancer cells [ xref ]." + + + +
+ + + +
+ + + + + + 32898953 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Furthermore, while the Wnt pathway does not initiate activation, the signaling components, β-catenin, and Lef1 , bind to the Pitx2 promotor and are subsequently required for maintaining Pitx2 expression." + + + +
+ + + +
+ + + + + + 33182738 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Indeed, functional activation of β-catenin-LEF1 was confirmed in the nail matrix just above the RSPO4 expressing mesenchyme (Fig. xref )." + + + +
+ + + +
+ + + + + + 34099859 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In the activated Wnt signaling pathway, LEF1 forms dimers with over-aggregated β-catenin." + + + +
+ + + +
+ + + + + + 36199361 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "YAP downregulation has been shown to sensitize BRAFi-resistant melanoma cells to MAPK pathway inhibitors, and YAP and Wnt signaling (via β-catenin-LEF1) co-regulate apoptosis of acquired MAPK inhibitor-resistant melanoma ( xref )." + + + +
+ + + +
+ + + + + + 34462276 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We showed that AEG-1 forms a complex with LEF1 and β-catenin, and AEG-1-mediated activation of Wnt/β-catenin pathway facilitated maintenance of glioma stem-like cells and their self-renewal ( xref )." + + + +
+ + + +
+ + + + + + 34353442 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The transient expression of Wnt1 induces the formation of β-catenin–LEF1 complex in nucleus, resulting in persistent activation of canonical Wnt/β-catenin signaling xref ." + + + +
+ + + +
+ + + + + + 36056132 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In the nucleus, β-Catenin binds to T cell factor lymphoid enhancer factor family to activate downstream genes, such as cyclin D1 and C-myc, leading to inhibition of the expression of PPARγ and CCAAT/enhancer binding protein-α (C/EBPα) ( xref ; xref ; xref ; xref )." + + + +
+ + + +
+ + + + + + 36188620 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Lef1 interacts with β-catenin to activate the transcription of the Wnt target genes [ xref , xref ]." + + + +
+ + + +
+ + + + + + 36140843 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "β-catenin which is then subsequently translocate to the nucleus interacts with T-cell factor and lymphoid enhancer factor (TCF/LEF)-family transcription factors ( xref ; xref ), initiating transcription of a set of pro-inflammatory, proliferative genes and oncogenes, such as CCND1 and MYC ( xref )." + + + +
+ + + +
+ + + + + + 34869313 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The effect of CGP049090 and PFK115-584, two compounds that specifically inhibit the binding between β-catenin and LEF1, was evaluated in Kasumi-1 and HL-60 AML cell lines, primary AML blasts and healthy peripheral blood mononuclear cells as a control." + + + +
+ + + +
+ + + + + + 31703382 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Wnt signaling promotes EC proliferation (Masckauchan et al., 2005, 2006) and the Lef1/Ctnnb1 complex induces cell cycle progression through transcriptional activation of Cyclin D1 (Shtutman et al., 1999)." + + + +
+ + + +
+ + + + + + 19154719 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "To quantitatively measure the ability of GATA4 to block interaction between β-catenin and LEF1/TCF1, we turned to bimolecular fluorescence complementation assay 34 by fusing β-catenin and LEF1/TCF1 to N- and C-terminal half of firefly luciferase respectively, such that when these fusion proteins were expressed in HepG2 cells, luciferase activity is a direct readout for interaction between β-catenin and LEF1/TCF1." + + + +
+ + + +
+ + + + + + 31903133 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Finally, β-catenin binds to TCF/LEF1 to replace the transcriptional suppressor Groucho in the target gene promoter, thereby regulating the expression of downstream target genes (c-Myc, Cyclin D1, etc.)." + + + +
+ + + +
+ + + + + + 32038289 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Nuclear DACT2 disrupts the interaction between β-catenin and LEF1, and cytoplasmic DACT2 represses β-catenin nuclear transport via restoring E-cadherin–β-catenin complex [80]." + + + +
+ + + +
+ + + + + + 32961708 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Chibby, a newly identified β-catenin antagonist, can disrupt the association between β-catenin and LEF1, and promotes β-catenin nuclear export via a chibby-14-3-3-β-catenin complex [81,82]." + + + +
+ + + +
+ + + + + + 32961708 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "When stimulated with Wnt or genetic mutations of Wnt components, β-catenin accumulates in the cytoplasm, translocates into the nucleus and binds to LEF-1/TCF4 and some other coregulators, leading to the expression of target genes, such as c-Myc and MMP7." + + + +
+ + + +
+ + + + + + 33893396 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In the context of cancer stemness, interactions between β-catenin and Lef1 transactivate the miR-371–373 cluster that mediates CSC self-renewal [ xref ]." + + + +
+ + + +
+ + + + + + 33817661 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "LEF1 binds to β-catenin to regulate the expression of downstream molecules, thereby regulating the signal pathway (42)." + + + +
+ + + +
+ + + + + + 34485109 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "However, there are clear discrepancies with the reported nuclear localisation of both β-catenin and the key canonical transcription factor lymphoid enhancer binding factor 1 (LEF1) in the pre-cortex [21,22] and the DP [20,23]." + + + +
+ + + +
+ + + + + + 29738529 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "SNAIL1 is a transcription factor usually expressed during EMT; its expression has been demonstrated to induces EMT in gastric cancer [ xref ] although it may direct the cells towards a low proliferating phenotype trough the β-catenin-LEF1 complex [ xref ]." + + + +
+ + + +
+ + + + + + 31906104 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Finally, crystal structure of β-catenin ARM repeats 2–10 with a bound part of Lef1 β-catenin-binding domain (β-catenin-BD) revealed that Lef1 interacts with β-catenin in an analogous manner as other members of TCF family." + + + +
+ + + +
+ + + + + + 32486423 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The bioinformatic analysis revealed an array of putative nuclear factor-binding sites, including two potential LEF1/TCF like elements located on -349 bp – -333 bp and +19 bp – +35 bp (Figure 2A), on which β-catenin acts as co-activator of TCF transcription factors to regulate the transcription of target genes.To determine whether β-catenin binds to the LEF1/TCF elements of PME-1 promoter, we performed the ChIP assay in SH-SY5Y cells." + + + +
+ + + +
+ + + + + + 31714894 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "We investigated whether inhibition of GSK-3β affects the binding of β-catenin with LEF1/TCF cis-elements." + + + +
+ + + +
+ + + + + + 31714894 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "We performed ChIP assay and found that ARA014418 treatment increased the levels of co-immunoprecipitated cis-elements of LEF1/TCF-1 and LEF1/TCF-2 by β-catenin (Figure 7A), suggesting inhibition of GSK-3β enhances the binding of β-catenin to LEF1/TCF elements.To determine the effect of ARA014418 on PME-1 expression in primary cultured cortical neurons, we treated the neurons with various concentrations of ARA014418 for 4.5 hr and analyzed mRNA level of PME-1 by qPCR." + + + +
+ + + +
+ + + + + + 31714894 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "We found that the promoter of human PME-1 contains two LEF1/TCF cis-elements, which act as enhancers to promote the expression of PME-1 and that binding of β-catenin to LEF1/TCF +cis-elements enhances the expression of PME-1." + + + +
+ + + +
+ + + + + + 31714894 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The interaction between beta-catenin, lymphoid enhancer-binding factor 1 (LEF1), and transcription factor 4 (TCF4) was studied in order to see its effects on melanoma." + + + +
+ + + +
+ + + + + + 31934531 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "It was observed that the increase in TCF4 and decrease in LEF1 was associated with an invasive transformation of melanoma, in contrast with epithelial tumors where the upregulation of beta-catenin interaction factor LEF1 was seen to promote EMT [89, 90]." + + + +
+ + + +
+ + + + + + 31934531 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In sphere cultures, we further observed that ectopic activation of WNT signaling using a β-catenin-LEF1 fusion protein xref (Fig.  xref ) triggered a strong induction of NOTCH signaling (Fig.  xref )." + + + +
+ + + +
+ + + + + + 32066735 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Moreover, PKF115-584 (that disrupts the interactions between β-catenin and LEF1, leading to transcriptional inactivation of LEF1) prevented and partially reverted leukemogenesis, by inducing apoptosis and reducing proliferation in human T-ALL cells [ xref ]." + + + +
+ + + +
+ + + + + + 32046053 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "This differential expression of the LEF isoform in LSC versus normal HSCs offers the opportunity to preferentially target LSCs by impairing LEF1-β-catenin interaction, and targeting Wnt/β-catenin axis." + + + +
+ + + +
+ + + + + + 32046053 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Moreover, PKF115-584 (that disrupts the interactions between β-catenin and LEF1, leading to transcriptional inactivation of LEF1) prevented and partially reverted leukemogenesis, by inducing apoptosis and reducing proliferation in human T-ALL cells [81]." + + + +
+ + + +
+ + + + + + 32046053 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "DACT2 has been reported to decrease LEF1-β-catenin binding in colon cancer by competing with β-catenin [ xref ]." + + + +
+ + + +
+ + + + + + 30359298 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Nuclear RAC1 in complex with β-catenin facilitates RAC1-dependent phosphorylation of β-catenin on serines 161 and 605, resulting in the formation of nuclear β-catenin-LEF-1, which is necessary for the transactivation of Wnt-dependent genes [ xref ]." + + + +
+ + + +
+ + + + + + 35013128 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Finally, based on the fact that certain vertebrate TCFs encode either repressor or activator function and that repressive TCF proteins have higher affinities for Gro/TLE, a model has been proposed by which Gro/TLE in complex with repressive TCFs (e.g., TCF3) is released upon Wnt signaling, allowing for the recruitment of activating TCFs (e.g., LEF1) bound to β-catenin [18]." + + + +
+ + + +
+ + + + + + 32759724 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In the classical Wnt/β-catenin pathway, β-catenin accumulates in the nucleus and binds to TCF1/LEF1 to promote downstream target gene expression." + + + +
+ + + +
+ + + + + + 31060551 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The Lef1 distal region is bound by β-catenin in WNT-stimulated ESCs but not in normal ESC culture conditions [ xref E, compare β-catenin (WNTa) versus β-catenin (control); data from xref ]." + + + +
+ + + +
+ + + + + + 36102628 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Nuclear beta-catenin and LEF1 were significantly associated with CTNNB1 mutation, showing nuclear beta-catenin a better specificity and positive predictive value for CTNNB1 mutation." + + + +
+ + + +
+ + + + + + 34420090 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "When LEF1 binds to beta-catenin, it activates epithelial-to-mesenchymal transition and cell proliferation [ xref ]." + + + +
+ + + +
+ + + + + + 34420090 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In response to Wnt signaling, LEF-1 bound to both DNA and β-catenin activates Wnt-responsive genes." + + + +
+ + + +
+ + + + + + 35177069 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In the nucleus, beta-catenin interaction with the transcriptional effectors TCF and LEF1 converts the latter from transcriptional repressors to activators." + + + +
+ + + +
+ + + + + + 24117889 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Dkk1 is thought to act as a soluble inhibitor for Wnt signaling [XREF_BIBR], while transcription factor Lef1 mediates Wnt signaling pathway by binding with its co-activator beta-catenin [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 29121993 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "On the other hand, beta-catenin present in the nucleus binds to Lef1 (k 49) to increase the expression of mRNA of Delta gene (k 54), followed by translation of Delta (k 51) and translocated to the cytoplasm (k 58)." + + + +
+ + + +
+ + + + + + 28106087 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "As a co-transactivator, β-catenin associates with the lymphoid enhancer factor (LEF)/T-cell factor (TCF) family of transcription factors and mediates expression of target genes involved in differentiation, polarization and cell fate xref ." + + + +
+ + + +
+ + + + + + 23418486 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Co-immunoprecipitation results indicated that DACT2 strongly associated β-catenin as well as lymphoid enhancer-binding factor 1 (LEF1) and directly disrupted the formation of the β-catenin-LEF1 complex in the nucleus." + + + +
+ + + +
+ + + + + + 25023701 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Activation of the Wnt and beta-catenin pathway is characterized by 1) stabilization of cytoplasmic beta-catenin after receptor engagement by Wnt ligands; 2) beta-catenin nuclear translocation, 3) beta-catenin interaction with lymphoid enhancer binding factor-1 and T-cell factor-1 (LEF and TCF) transcription factors; and 4) stimulation of target genes." + + + +
+ + + +
+ + + + + + 28838333 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "DACT2 was reported to promote Dvl degradation in a lysosome dependent pathway, and inhibits LEF1 binding to beta-catenin [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 22806826 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The potential explanation is that DACT2 promotes Dvl degradation in a lysosome dependent pathway and inhibits LEF1 binding to beta-catenin [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 22806826 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "DACT2 was reported to promote Dvl degradation in a lysosome-dependent pathway, and inhibits LEF1 binding to β-catenin [ xref ]." + + + +
+ + + +
+ + + + + + 22806826 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The potential explanation is that DACT2 promotes Dvl degradation in a lysosome-dependent pathway and inhibits LEF1 binding to β-catenin [ xref ]." + + + +
+ + + +
+ + + + + + 22806826 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "They antagonize the Wnt pathway by decreasing the cellular beta-catenin, disrupting the beta-catenin and LEF -1 complexes, and repressing the Wnt target genes [XREF_BIBR, XREF_BIBR, XREF_BIBR - XREF_BIBR]." + + + +
+ + + +
+ + + + + + 23213540 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Coimmunoprecipitation showed a selective disruption of beta-catenin and LEF -1 interaction." + + + +
+ + + +
+ + + + + + 23213540 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The cytoplasmic tails of N- or E-cadherin colocalized with beta-catenin in the nucleus, and suppressed the constitutive LEF-1-mediated transactivation, by blocking beta-catenin-LEF-1 interaction." + + + +
+ + + +
+ + + + + + 9860970 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Interactions between beta-catenin and LEF-1 and TCF, APC and conductin and axin are essential for wnt controlled stabilization of beta-catenin and transcriptional activation." + + + +
+ + + +
+ + + + + + 10966653 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Activation of the Wnt/β-catenin pathway is characterized by 1) stabilization of cytoplasmic β-catenin after receptor engagement by Wnt ligands; 2) β-catenin nuclear translocation, 3) β-catenin interaction with lymphoid enhancer-binding factor-1/T-cell factor-1 (LEF/TCF) transcription factors; and 4) stimulation of target genes ( xref – xref )." + + + +
+ + + +
+ + + + + + 28838333 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The nuclear β-catenin interacts with the transcription factor LEF1 to activate target gene expression ()." + + + +
+ + + +
+ + + + + + 16890162 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "These results suggest that Tob1a inhibits the interaction between β-catenin and LEF1 solely by competing with LEF1 for β-catenin." + + + +
+ + + +
+ + + + + + 16890162 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Furthermore, we demonstrate that TGFbeta dependent activation of LEF1 and TCF target genes can occur in the absence of beta-catenin binding to LEF1 and TCF and requires both Smad and LEF1 and TCF DNA binding sites in the Xtwn promoter." + + + +
+ + + +
+ + + + + + 10890911 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Here we propose that the beta-catenin nuclear import pathway may provide an opportunity for identification of specific drug targets and inhibition of beta-catenin nuclear function, much like the current screening of drugs that block binding of beta-catenin to LEF-1 and TCFs." + + + +
+ + + +
+ + + + + + 24820952 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Lithium favours lymphoid enhancer factor-1/beta-catenin binding to Gip promoter and diminishes ChIP through T cell factor-4 and histone deacetylase 1." + + + +
+ + + +
+ + + + + + 19582394 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "14 Wnt stabilizes cytosolic beta-catenin, which then binds to TCF and LEF1 in the nucleus and recruits transcription factors Brg1 and CREB binding protein to initiate Wnt targeted gene expression." + + + +
+ + + +
+ + + + + + 28277542 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "As beta-catenin binds to LEF1 in the nucleus in the Wnt-canonical pathway, we performed beta-catenin immunostaining." + + + +
+ + + +
+ + + + + + 28693719 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "It has been shown that phosphorylated β-catenin can interact with LEF-1 but cannot form a ternary complex with DNA xref and cannot drive TCF reporter activity xref ." + + + +
+ + + +
+ + + + + + 20862283 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "While beta-catenin can bind directly to both AR and Lef1, GRIP1 can only bind directly to AR; the ability of GRIP1 to associate with and function as a coactivator for Lef1 is entirely dependent on the presence of beta-catenin." + + + +
+ + + +
+ + + + + + 14638683 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "As β-catenin binds to LEF1 in the nucleus in the Wnt-canonical pathway ( xref ), we performed β-catenin immunostaining." + + + +
+ + + +
+ + + + + + 28693719 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The result confirmed the tight association between beta-catenin and LEF-1 in the nucleus, further confirming activation of the Wnt signaling (XREF_FIG)." + + + +
+ + + +
+ + + + + + 22391957 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In this study, it was observed that the overexpression of wild type LEF1, which can interact with β-catenin, decreased the endogenous levels of Notch1 in a dose-dependent manner (left panel of A)." + + + +
+ + + +
+ + + + + + 19000719 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Chromatin immunoprecipitation (ChIP) analysis also showed that the T-cell factor (TCF)4, which is one of the transcription factors of the lymphoid enhancer factor (LEF)/TCF family that binds to stabilized β-catenin to regulate Wnt signalling xref , is bound to the promoter of Irs1 xref ." + + + +
+ + + +
+ + + + + + 27708333 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Wnt factors including beta-catenin, glycogen synthase kinase (GSK3) beta, the lymphoid enhancer binding factor 1 (LEF1) and cyclin D1 have been identified as interacting with the androgenic signaling axis [XREF_BIBR, XREF_BIBR]." + + + +
+ + + +
+ + + + + + 23667383 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "LEF1 interacts with beta-catenin and plays critical role in proliferation of RCC by activating downstream target genes [XREF_BIBR, XREF_BIBR]." + + + +
+ + + +
+ + + + + + 27766950 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "LEF1 interacts with β-catenin and plays critical role in proliferation of RCC by activating downstream target genes [ xref , xref ]." + + + +
+ + + +
+ + + + + + 27766950 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "β-catenin may increase FoxO transcriptional activity and competitively limit β-catenin interaction with members of the lymphoid enhancer factor/T cell factor family. xref This may lead to cell injury, since β-catenin has been demonstrated to be necessary for protection against Aβ toxicity in neuronal cells. xref " + + + +
+ + + +
+ + + + + + 20716915 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Wnt/β-catenin pathway activation is characterized by (i) stabilization of cytoplasmic β-catenin upon receptor engagement by Wnt ligands, (ii) β-catenin nuclear translocalion, (iii) β-catenin interaction with lymphoid enhancer-binding factor-1/T-cell factor-1 (LEF/TCF) transcription factors, and (iv) stimulation of target genes xref , xref ." + + + +
+ + + +
+ + + + + + 20852629 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Beta-catenin and TCF -1 pathway in T cell development and differentiation : The discovery of the association between beta-catenin and LEF-1 set the stage for the realization that beta-catenin is found in the nucleus and has a role as a transcriptional co-regulator." + + + +
+ + + +
+ + + + + + 23114888 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Moreover, RAC1 nuclear accumulation in complex with β-catenin occurs following Wnt or RAC1 activation, resulting in RAC1-dependent phosphorylation of β-catenin on serines 161 and 605, promoting the formation of nuclear β-catenin-lymphoid enhancer factor (LEF-1) complexes, necessary for transactivation of Wnt-dependent genes [ 42 ]." + + + +
+ + + +
+ + + + + + 29723737 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "This allows the direct interaction of β-catenin with the lymphoid enhancer factor-T cell factor family of transcription factors and the promotion of cells into the cell cycle ( xref )." + + + +
+ + + +
+ + + + + + 24765201 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "On the other hand, interactions between Runx2 and beta-catenin and Lef1 inhibit Runx2 mediated activation of osteocalcin [XREF_BIBR], and Runx3 was recently shown to attenuate tumorogenic beta-catenin signaling via direct physical interactions with both beta-catenin and TCF4 [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 19330799 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The bHLH-LZ region of MITF-M is responsible for the physical interaction with LEF-1, and beta-catenin is required for the collaboration between LEF-1 and MITF-M. Importantly, MITF-M could function as a non-DNA-binding co-factor for LEF-1." + + + +
+ + + +
+ + + + + + 12753399 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Nuclear β-catenin interacts with members of the Lymphoid Enhancer Factor/T-cell factor (LEF/TCF) family of transcription factors and also with Legless family docking proteins BCL9/BCL9L, which associate with the transcription co-activator pygopus (PYGO) 1/2 ( xref )." + + + +
+ + + +
+ + + + + + 20200414 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Interaction of β-catenin with transcription factors of the lymphoid enhancer-binding factor/T cell factor family in the nucleus subsequently regulate the transcription of Wnt target genes ( xref )." + + + +
+ + + +
+ + + + + + 19723499 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Subsequent EMSA and ChIP analysis confirmed the binding of Ets-1 and LEF-1 and beta-catenin transcription factors to the predicted sites." + + + +
+ + + +
+ + + + + + 22952895 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Regarding the putative role of the LEF1 gene in hernia, it has been shown that the LEF1 protein constitutively associates with beta-catenin which mediates the action of the anti-mullerian hormone (AMH) [XREF_BIBR], itself involved in the gubernaculum swelling reaction that occurs during the first phase of testicular descent [XREF_BIBR, XREF_BIBR]." + + + +
+ + + +
+ + + + + + 25886970 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Regarding the putative role of the LEF1 gene in hernia, it has been shown that the LEF1 protein constitutively associates with β-catenin which mediates the action of the anti-mullerian hormone (AMH) [ xref ], itself involved in the gubernaculum swelling reaction that occurs during the first phase of testicular descent [ xref , xref ]." + + + +
+ + + +
+ + + + + + 25886970 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 12748295 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 15684397 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 10890911 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 8757136 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 8757136 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 16510874 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 16510875 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 16204248 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 10958684 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 11835406 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 15525529 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 11751639 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 12077367 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 18296023 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 15768032 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 9419974 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 9419974 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 15728254 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 21743491 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 21743491 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 12556497 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 8757136 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 15684397 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "MALDI-TOF mass spectrometry (MS) identified two CK2 phosphorylation sites (S42, S61) within the amino terminus of hLEF-1, and mutation of these sites reduced binding to beta-catenin in vitro and transactivation in vivo." + + + +
+ + + +
+ + + + + + 17113388 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "MALDI-TOF mass spectrometry (MS) identified two CK2 phosphorylation sites (S42, S61) within the amino terminus of hLEF-1, and mutation of these sites reduced binding to beta-catenin in vitro and transactivation in vivo." + + + +
+ + + +
+ + + + + + 17113388 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "MALDI-TOF mass spectrometry (MS) identified two CK2 phosphorylation sites (S42, S61) within the amino terminus of hLEF-1, and mutation of these sites reduced binding to beta-catenin in vitro and transactivation in vivo." + + + +
+ + + +
+ + + + + + 17113388 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "To develop an enzyme linked immunosorbent assay (ELISA)-based high throughput screening (HTS) method for beta-catenin and Lef1 interaction antagonists screening, Escherichia coli Rosetta (DE3) competent cells were transformed with beta-catenin-pET-30a (+) plasmid." + + + +
+ + + +
+ + + + + + 31001956 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Taken together, we have successfully developed a simple, robust and reliable ELISA based HTS method for screening of novel Wnt inhibitors targeting beta-catenin and Lef1 interaction." + + + +
+ + + +
+ + + + + + 31001956 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In the nucleus, β-catenin interacts with members of the lymphoid enhancer factor/T cell factor (LEF/TCF) protein family () and also with other transcription factors, such as Forkhead box protein O1 (FoxO1), hypoxia-inducible factor (HIF), Smads, and others (for review, see )." + + + +
+ + + +
+ + + + + + 24044891 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Beta-catenin bound the transcription factors Tcf7 and Lef1, which promoted transcription of targeted genes, as evidenced by the increased gene expression of Jun, Fzd7, and Nlk after TWS119 treatment." + + + +
+ + + +
+ + + + + + 31119051 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Other work has shown that c-KIT stabilises β-catenin expression [ xref ] which forms a complex with LEF-1 to induce cyclin D1 expression [ xref ]." + + + +
+ + + +
+ + + + + + 27769165 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "When LEF-1 interacts with CTNNB1, it leads to upregulation of LEF-1 in SPN." + + + +
+ + + +
+ + + + + + 30283597 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "When LEF-1 interacts with CTNNB1, it leads to upregulation of LEF-1 in SPN." + + + +
+ + + +
+ + + + + + 30283597 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Nuclear translocation of beta-catenin binds to the DNA binding proteins Tcf and Lef1 that subsequently regulates target genes including CyclinD1 important in proliferation." + + + +
+ + + +
+ + + + + + 22391317 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "We recently identified and characterized a novel Wnt like effect of transforming growth factor-beta (TGF-beta) on beta-catenin, the binding partner of Lef-1." + + + +
+ + + +
+ + + + + + 15736165 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Maetzel et al ( xref ) firstly demonstrated that a proteolytic fragment of EpCAM containing EpICD forms a complex with β-catenin and LEF-1, which translocates to the nucleus and activates the transcription of genes associated with cell proliferation, such as c-Myc and cyclins A and E, thereby promoting oncogenesis ( xref ) ( xref )." + + + +
+ + + +
+ + + + + + 30015855 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The two pathways were found to converge at the promoter of Xtwn, where Smad4, beta-catenin, and Lef1 form a complex and bind to adjacent regulatory elements to co-regulate Xtwn expression." + + + +
+ + + +
+ + + + + + 19002158 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "have demonstrated that in vitro transcriptional activation by recombinant beta-catenin and LEF -1 complexes requires ubiquitin." + + + +
+ + + +
+ + + + + + 21118991 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Here, we present ITC measurements of Lef-1 and Tcf4 binding to beta-catenin under identical conditions, which show that Lef-1 binds slightly less strongly than Tcf4 to beta-catenin." + + + +
+ + + +
+ + + + + + 21075118 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The extended N-terminal region of Lef-1 binds to beta-catenin using most of the conserved sequence motif Dxthetathetaxphix 2-7 E." + + + +
+ + + +
+ + + + + + 21075118 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Given the difference in the structures of TCF-4 and Lef-1 bound to beta-catenin, it was of interest to compare the thermodynamics of these complexes." + + + +
+ + + +
+ + + + + + 21075118 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "However, clinical targeted treatment of the beta-catenin and LEF -1 complex remains relatively ineffective." + + + +
+ + + +
+ + + + + + 26750754 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Thus, we attempted to synthesize a peptide (TAT-NLS-BLBD-6) that could interfere with the interaction of beta-catenin and LEF-1 at nuclei in human breast cancer cells." + + + +
+ + + +
+ + + + + + 26750754 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The beta-catenin and LEF -1 complex is a nuclear response transcription factor and plays an important role in the Wnt and wingless signaling pathway XREF_BIBR." + + + +
+ + + +
+ + + + + + 26750754 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Otherwise, upon Wnt binding to the receptor complex, beta-catenin translocates to the nucleus and binds with the LEF-1 and TCF co-transfection factor." + + + +
+ + + +
+ + + + + + 26750754 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In the current study, we synthesized a small peptide to block the interaction between beta-catenin and LEF-1." + + + +
+ + + +
+ + + + + + 26750754 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In our current study, we synthesized a small peptide TAT-NLS-BLBD-6 (ATDEMIPF), which is a Wnt and beta-catenin signaling inhibitor and prevents the binding of beta-catenin to LEF-1 at the nuclear region of human breast cancer cells." + + + +
+ + + +
+ + + + + + 26750754 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In summary, our study found that TAT-NLS-BLBD-6, a cell penetrating pentapeptide, blocks the interaction between beta-catenin and LEF-1 and also efficiently attenuates tumorigenesis in vitro and in vivo." + + + +
+ + + +
+ + + + + + 26750754 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "These results provide evidence that Lef1 promoted the differentiation of bulge stem cells into a hair fate and interacted directly with beta-catenin." + + + +
+ + + +
+ + + + + + 23630438 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "We also report that Lef1 could bind to beta-catenin directly and translocate it into the nucleus, resulting in the activation of the Wnt signaling pathway." + + + +
+ + + +
+ + + + + + 23630438 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "There is evidence that beta-catenin can act as a nuclear import receptor to induce the nuclear translocation of Lef1 XREF_BIBR, indicating a close interaction between Lef1 and beta-catenin." + + + +
+ + + +
+ + + + + + 23630438 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In vitro phosphorylation of purified Lef-1 was used to examine the effect of CK2 on the interaction of Lef-1 with β-catenin." + + + +
+ + + +
+ + + + + + 21075118 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Isothermal titration calorimetry revealed that β-catenin binds to non-phosphorylated or CK2 phosphorylated Lef-1 with the same affinity, which is consistent with the absence of phosphoSer40 interactions in the crystal structure of phosphorylated Lef-1 N-terminal domain bound to β-catenin." + + + +
+ + + +
+ + + + + + 21075118 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "These data indicate that the effect of CK2 on the Wnt/β-catenin pathway does not appear to be at the level of the Lef-1–β-catenin interaction." + + + +
+ + + +
+ + + + + + 21075118 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In order to compare the interactions of Tcf family members with β-catenin, we have determined crystal structures of non-phosphorylated and CK2-phosphorylated Lef-1 bound to the armadillo domain of β-catenin and Lef-1." + + + +
+ + + +
+ + + + + + 21075118 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We also find that CK2 phosphorylation of Lef-1 produces no change in affinity or in the structure of the complex, indicating that the effects of CK2 on β-catenin-mediated transcription are not at the level of the Lef-1–β-catenin interaction." + + + +
+ + + +
+ + + + + + 21075118 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The extended N-terminal region of Lef-1 binds to β-catenin using most of the conserved sequence motif Dxθθxφx 2–7 E. There are relatively few direct contacts between Lef-1 residues 11–18 and β-catenin, which include a salt bridge between Asp12 and Arg515, and the backbone carbonyl oxygen of Gly11 forms a hydrogen bond with Arg582 ( xref )." + + + +
+ + + +
+ + + + + + 21075118 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In order to assess the possible effects of CK2 phosphorylation on the Lef-1–β-catenin interaction, the complex of the CK2-phosphorylated Lef-1(1–63) and β-cat-arm was purified and crystallized." + + + +
+ + + +
+ + + + + + 21075118 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In this smaller lattice, Lef-1 Asp26, Gly28, Pro30, Gln31, Glu33, Phe36, Ala37, and Glu38 interact directly with neighboring β-catenin molecules ( xref ); note that Glu33 forms a salt bridge with Arg647 of a neighbor as well as Arg386 (see above)." + + + +
+ + + +
+ + + + + + 21075118 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Residues 11–18 adopt a conformation different from the equivalent portions of other Tcfs, which may be due to differences in lattice packing, as neighboring molecules of β-catenin interact with some of this region of Lef-1. (Interestingly, pLef-1 Cys16 forms a disulfide bond with β-catenin Cys350 from a lattice neighbor, even though its conformation is the same in the non-phosphorylated structure.) It is also possible that some of the difference arises from the insertion of Pro13 between two acids that are otherwise adjacent in sequence in the other Tcfs ( xref ); Lef-1 Asp12 forms a salt bridge with β-catenin Arg515 ( xref ), whereas the equivalent interaction is absent in other TCF–β-catenin structures." + + + +
+ + + +
+ + + + + + 21075118 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In such treated cells, the association of beta-catenin with Lef-1 and the transcription of c-myc, cyclin-D1, CD44 and COX-2 were also reduced." + + + +
+ + + +
+ + + + + + 16080193 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "As shown in XREF_FIG, a clear less associated LEF1 was observed in beta-catenin precipitates from DACT2 expressing cells, indicating that the interaction between LEF1 and beta-catenin was evidently impaired in the presence of DACT2." + + + +
+ + + +
+ + + + + + 25023701 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The interaction between beta-catenin and LEF-1 and TCF transcription factors plays a pivotal role in the Wnt-1 signaling pathway." + + + +
+ + + +
+ + + + + + 9874785 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We also report that Lef1 could bind to β-catenin directly and translocate it into the nucleus, resulting in the activation of the Wnt signaling pathway." + + + +
+ + + +
+ + + + + + 23630438 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "There is evidence that β-catenin can act as a nuclear import receptor to induce the nuclear translocation of Lef1 xref , indicating a close interaction between Lef1 and β-catenin." + + + +
+ + + +
+ + + + + + 23630438 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Because LEF-1 possesses its own NLS ( Huber et al., 1996 ) and is able to interact with β-catenin, we asked whether glucose favored LEF-1 and β-catenin interaction as a possible mechanism for the nuclear accumulation of β-catenin." + + + +
+ + + +
+ + + + + + 23273980 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Immunoprecipitation experiments indicated that LiCl and glucose cooperate to selectively favor nuclear LEF-1 and β-catenin interaction, and neither glucose nor LiCl alone allowed complex formation ( Figure 2 D)." + + + +
+ + + +
+ + + + + + 23273980 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Whereas ectoptic WT β-catenin bound p300 upon exposure of the cells to both glucose and LiCl (like endogenous β-catenin), conditions that promote LEF-1 and β-catenin interaction and nuclear accumulation of β-catenin, the Δ19 β-catenin mutant was unable to bind p300 under any conditions." + + + +
+ + + +
+ + + + + + 23273980 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Thus, the LEF-1 and β-catenin interaction promoted by the combination of glucose and LiCl appears critical for stabilizing p300 interaction and nuclear retention." + + + +
+ + + +
+ + + + + + 23273980 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "At the GIP , GCG , and cyclin D promoters, both LEF-1 and β-catenin were poorly bound in the absence of LiCl." + + + +
+ + + +
+ + + + + + 23273980 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Single treatment with glucose or LiCl alone induced only minor increases in the binding of both LEF-1 and β-catenin." + + + +
+ + + +
+ + + + + + 23273980 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Increased binding of both LEF-1 and β-catenin at the cyclin D promoter follows combined treatment with glucose and LiCl in HT-29 colon cancer cells." + + + +
+ + + +
+ + + + + + 23273980 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "First, it increases p300 expression and enhances its interactions with LEF-1 and β-catenin; second, it inhibits sirtuin deacetylase activity." + + + +
+ + + +
+ + + + + + 23273980 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "K354 lies within the region absent in the Δ19 mutant, a region previously identified as being critical for β-catenin interaction with LEF-1 ( von Kries et al., 2000 )." + + + +
+ + + +
+ + + + + + 23273980 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Although the precise molecular mechanisms have not been explored here, we view it as probable that SIRT1 acts as a competitor for interaction between LEF-1 and β-catenin." + + + +
+ + + +
+ + + + + + 23273980 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Although SIRT1 may play a role via stable and direct binding to LEF-1 or β-catenin, it is also clear that its catalytic activity is particularly important." + + + +
+ + + +
+ + + + + + 23273980 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "XREF_BIBR While collectively these measurements reveal that phosphorylated APC competes effectively with LEF and TCF for beta-catenin binding, recent data suggests phosphorylation of LEF-1 by CK2 also enhances LEF-1 binding to beta-catenin." + + + +
+ + + +
+ + + + + + 19928349 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "APC binds to CK2 and renders it inactive, leaving LEF-1 in an unphosphorylated form and thereby less able to bind beta-catenin." + + + +
+ + + +
+ + + + + + 19928349 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Jerky also recruits β-catenin to chromatin, and promotes the association of β-catenin and LEF1, resulting in the induction of Wnt target gene expression.( xref , xref ) We found that RUNX3 increases the occupancy of the TCF4/β-catenin complex in KatoIII cells, suggesting that RUNX3 plays a role in the stabilization of the TCF4/β-catenin complex on the Wnt target gene promoter like TBL1 and Jerky." + + + +
+ + + +
+ + + + + + 24447505 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In this study, HT-29 colon cancer cells with truncated APC have LEF-1 and beta-catenin complexes constitutively occupying a WRE in the cMYC enhancer." + + + +
+ + + +
+ + + + + + 19460168 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Here we show, in a yeast two-hybrid screen, that the architectural transcription factor LEF-1 (for lymphoid enhancer binding factor) interacts with beta-catenin." + + + +
+ + + +
+ + + + + + 8757136 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In relation to this, it is notable that although lymphoid enhancer factor/TCF7 transcription factors associate with β-catenin in canonical wnt signaling leading to the transcription of its target genes, SATB1 has recently been shown to competitively influence the TCF7 binding to β-catenin ( xref )." + + + +
+ + + +
+ + + + + + 20467038 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Lef1 can interact with beta-catenin in a transcriptional complex downstream of Wnt signaling XREF_BIBR, and this pathway antagonizes aspects of testis development XREF_BIBR, XREF_BIBR." + + + +
+ + + +
+ + + + + + 22438826 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Association of LEF-1 with β-catenin relieves this inhibition and facilitates LEF-1 interaction with chromatin ." + + + +
+ + + +
+ + + + + + 12067647 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Lef1 can interact with β-catenin in a transcriptional complex downstream of Wnt signaling xref , and this pathway antagonizes aspects of testis development xref , xref ." + + + +
+ + + +
+ + + + + + 22438826 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In transgenic mouse models, intact Wnt signaling promotes hair follicle differentiation, whereas inhibition of Wnt signaling through the prevention of Lef1 and beta-catenin interaction leads to sebocyte differentiation." + + + +
+ + + +
+ + + + + + 26548488 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Here we show, in a yeast two-hybrid screen, that the architectural transcription factor LEF-1 (for lymphoid enhancer-binding factor) interacts with beta-catenin." + + + +
+ + + +
+ + + + + + 8757136 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In mammalian cells, coexpressed LEF-1 and beta-catenin form a complex that is localized to the nucleus and can be detected by immunoprecipitation." + + + +
+ + + +
+ + + + + + 8757136 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Moreover, LEF-1 and beta-catenin form a ternary complex with DNA that splays an altered DNA bend." + + + +
+ + + +
+ + + + + + 8757136 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In vivo, MuSCs underwent a switch from β-catenin-Lef1 to Smad3-Lef1 interactions during the postnatal switch from proliferation to quiescence, with β-catenin-Lef1 interactions recurring during damage-induced reactivation." + + + +
+ + + +
+ + + + + + 30042129 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Further, a significant difference in the interaction between Lef1 and beta-catenin was seen when wild-type cells were compared with knockout cells (XREF_FIG)." + + + +
+ + + +
+ + + + + + 27903773 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In NLK-knockout cells, there is a constitutive interaction between Lef1 and beta-catenin, which could explain the elevated Tcf/Lef promoter activity in these cells." + + + +
+ + + +
+ + + + + + 27903773 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Previous studies have found that members of the lymphoid enhancer factor-1/T-cell factor (LEF-1/TCF) family interaction with β-catenin and their roles as the nuclear effectors of Wnt signaling [ xref , xref ]." + + + +
+ + + +
+ + + + + + 27835604 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In NLK-knockout cells, we observed sustained interaction between Lef1 and β-catenin, leading to elevated luciferase reporter of β-catenin/Lef1–mediated transcriptional activation." + + + +
+ + + +
+ + + + + + 27903773 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Further, a significant difference in the interaction between Lef1 and β-catenin was seen when wild-type cells were compared with knockout cells ( xref )." + + + +
+ + + +
+ + + + + + 27903773 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "LEF-1 and β-catenin form a ternary complex with DNA that displays an altered DNA bend ( xref )." + + + +
+ + + +
+ + + + + + 19458225 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Nuclear beta-catenin binds to and activates the LEF-1 and TCF transcription factors to induce expression of genes involved in tumorigenicity and invasion." + + + +
+ + + +
+ + + + + + 11535620 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Beta-catenin then accumulates in the nucleus and binds LEF-1 and TCF to regulate the expression of Wnt target genes." + + + +
+ + + +
+ + + + + + 25311420 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Functional interaction of beta-catenin with the transcription factor LEF-1." + + + +
+ + + +
+ + + + + + 8757136 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "It was shown that Smad4, beta catenin and Lef1 form a complex to activate expression of the Wnt target gene twin (Xtwn) [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 19926329 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The downregulation of APC contributes to nuclear accumulation of β-catenin, which subsequently interacts with the lymphoid enhancing factor/T cell factor (TCF) transcription factor to activate the transcription of target genes including c-Myc, cyclin D1, and matrix metalloproteinase 7 (MMP7) [ xref ]." + + + +
+ + + +
+ + + + + + 30134915 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Thus, unlike polarized cells, in mesenchymal cells LEF-1 and beta-catenin may form complexes within the nucleus." + + + +
+ + + +
+ + + + + + 10629227 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Moreover, a LEF-1 and TCF recognition site has been identified upstream of these elements, which was shown to bind to a beta-catenin and LEF -1 complex in vitro (Huber et al. 1996b)." + + + +
+ + + +
+ + + + + + 10629227 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "It remains to be determined whether beta-catenin and LEF -1 complexes recognize this site also in vivo and whether they influence the expression of E-cadherin in a positive or negative fashion." + + + +
+ + + +
+ + + + + + 10629227 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "As many of these structures were also stained by an affinity purified anti-LEF-1 antibody, they likely represent functional beta-catenin and LEF -1 complexes." + + + +
+ + + +
+ + + + + + 10629227 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The notion that transcriptionally active beta-catenin and LEF -1 complexes were formed in estradiol treated FosER cells was supported by our observation that LEF-1 and TCF-dependent luciferase reporter activity was clearly elevated in the mesenchymal cells." + + + +
+ + + +
+ + + + + + 10629227 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Thus, activation of FosER and integrin linked kinase might trigger signaling pathways that are linked to the wnt-pathway or regulate the formation of an active nuclear beta-catenin and LEF -1 complex via as yet unknown mechanisms." + + + +
+ + + +
+ + + + + + 10629227 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Thus, unlike polarized cells, in mesenchymal cells LEF-1 and β-catenin may form complexes within the nucleus." + + + +
+ + + +
+ + + + + + 10629227 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Our results clearly demonstrated that endogenous β-catenin and endogenous LEF-1/TCF proteins in mesenchymal FosER cells were able to form a transcriptionally active complex, which could be increased further upon ectopic expression of β-catenin and LEF-1 without additional signals." + + + +
+ + + +
+ + + + + + 10629227 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In addition to TCF4 mainly (Gotoh et al. xref ), LEF-1 (Grueneberg et al. xref ), HBP1 (Sampson et al. xref ), and UBF2 (Grueneberg et al. xref ) can also affect the cyclin D1 promoter activity by interaction with β-catenin or LEF-1." + + + +
+ + + +
+ + + + + + 22704330 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "However, EpICD does not only interact with β-catenin and Lef-1, it also binds to Lef-1 consensus sites in the promoter of Wnt target genes such as cyclin D1." + + + +
+ + + +
+ + + + + + 24944998 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The interaction between the enamelin elements and beta-catenin and LEF1 was further confirmed by electrophoresis mobility shift assays and chromatin immunoprecipitation assays." + + + +
+ + + +
+ + + + + + 20599763 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Over-expression of ILK in intestinal epithelial cells resulted in the expression of an invasive phenotype, which is consistent with Wnt pathway events such as loss of E-cadherin expression, and nuclear translocation of β-catenin, formation of a lymphoid enhancer factor (LEF)-1/β-catenin complex, and enhanced LEF-1 transcriptional activity (Novak et al., 1998) ." + + + +
+ + + +
+ + + + + + 12191615 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Recent implications for beta-catenin signaling in cancer prompted us to examine colon cancer cell lines for the expression of LEF-1, a transcription factor that binds to beta-catenin." + + + +
+ + + +
+ + + + + + 9419974 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Beta-catenin binds TCF-4 or LEF-1 to regulate cognate gene expression." + + + +
+ + + +
+ + + + + + 21744004 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In these cells, the association of endogenous LEF1 and beta-catenin was induced by stimulation with the wnt-1 proto-oncogene." + + + +
+ + + +
+ + + + + + 9419974 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Ectopic overexpression of beta-catenin in 293 cells also induced the assembly of the beta-catenin-LEF-1 complex and activated gene transcription from a LEF-1-dependent promotor." + + + +
+ + + +
+ + + + + + 9419974 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The results suggest that a cancer pathway driven by wnt-1, or mutant forms of beta-catenin, may involve the formation of a persistent transcriptionally active complex of beta-catenin and LEF1." + + + +
+ + + +
+ + + + + + 9419974 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "To activate target gene expression, TCF-1 and LEF-1 must first associate with beta-catenin." + + + +
+ + + +
+ + + + + + 23041833 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "[Development of an ELISA based high throughput screening method for novel anticancer agents targeting beta-catenin and Lef1 interaction]." + + + +
+ + + +
+ + + + + + 31001956 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Since APC and the HMG transcription factor Lef-1 both bind to the armadillo repeats of beta-catenin, beta-catenin must dissociate from APC and subsequently bind to Lef-1 to allow translocation to the nucleus and transcriptional activation." + + + +
+ + + +
+ + + + + + 9362521 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Since APC and the HMG transcription factor Lef-1 both bind to the armadillo repeats of β-catenin ( xref ; xref ), β-catenin must dissociate from APC and subsequently bind to Lef-1 to allow translocation to the nucleus and transcriptional activation." + + + +
+ + + +
+ + + + + + 9362521 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "It is possible that α-catenin could abrogate monomeric β-catenin's association with Lef-1 or alternatively stabilize β-catenin's association in the APC complex." + + + +
+ + + +
+ + + + + + 9362521 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Some studies reported promising results in APC mutated CRC cell lines [XREF_BIBR, XREF_BIBR], whilst others showed that nuclear beta-catenin bound to LEF-1 and TCF transcription factors would be protected from degradation such that TNKSi treatment would not be effective [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 26930278 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Accumulated unphosphorylated β-catenin translocates to the nucleus and eventually binds to the lymphoid enhancer factor/T cell factor (LEF/TCF) transcription factors to exert effects on downstream gene transcription." + + + +
+ + + +
+ + + + + + 29361730 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Further analysis revealed that SMAR1 overexpression led to Wnt3a dependent TCF4/LEF1 transcriptional inhibition by reducing the association of β-catenin and LEF1 ( xref )." + + + +
+ + + +
+ + + + + + 29765542 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "hESCs treated with Wnt3A for 6 hours showed rapid binding of beta-catenin and LEF1 to the LGR5 locus as well, indicating that LGR5 is a direct target of these transcription factors (XREF_FIG D)." + + + +
+ + + +
+ + + + + + 28078320 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "This process results in activation of β-catenin-regulated transcription (CRT), which interacts with transcription factors lymphoid enhancer factor (LEF)/T-cell factor (TCF)." + + + +
+ + + +
+ + + + + + 31867287 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Approaches impairing binding of LEF1 to β-catenin significantly impaired AML growth, but spared normal hematopoietic stem cells." + + + +
+ + + +
+ + + + + + 31758089 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The cytoplasmic accumulation of β-catenin after activation of Wnt signaling, or the release of β-catenin due to the loss of E-cadherin, which allow the interactions between β-catenin and LEF-1, can induce the upregulation of Snail, Slug, Twist and mesenchymal markers such as fibronectin ( xref ; xref )." + + + +
+ + + +
+ + + + + + 31849690 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Approaches impairing binding of LEF1 to beta-catenin significantly impaired AML growth, but spared normal hematopoietic stem cells." + + + +
+ + + +
+ + + + + + 31758089 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "This report now demonstrates a striking difference of LEF1 isoform expression between normal and AML cells, contributing to higher vulnerability of leukemic cells to approaches targeting beta-catenin and LEF1 interaction." + + + +
+ + + +
+ + + + + + 31758089 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In this report, we present evidence that canonical Wnt and beta-catenin signaling is not required for initial activation of Pitx2, but it is required for maintenance of its continued expression likely via direct binding of Lef-1 and beta-catenin to the Pitx2 promoter." + + + +
+ + + +
+ + + + + + 20960542 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The binding of unphosphorylated beta-catenin to Lef1 in the nucleus to form the transcription activator was modeled using a mass action law (Eq2.11 in the Additional file XREF_SUPPLEMENTARY)." + + + +
+ + + +
+ + + + + + 23602012 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Research by Juan Galceran et al. [XREF_BIBR] confirmed that Lef1 binds to beta-catenin in the nucleus to form the Lef1, beta, and catenin complex that activates the expression of endogenous Dll1 in fibroblasts." + + + +
+ + + +
+ + + + + + 23602012 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Using recombinant proteins, we found that E-cadherin and lymphocyte-enhancer factor-1 (LEF-1) form mutually exclusive complexes with beta-catenin; the association of beta-catenin with LEF-1 was competed out by the E-cadherin cytoplasmic domain." + + + +
+ + + +
+ + + + + + 10085258 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In all SCOUTs the expression of LEF1 was associated with a marked +nuclear expression of β-catenin ( xref )." + + + +
+ + + +
+ + + + + + 28664938 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Further, chromatin immunoprecipitation (ChIP) assays demonstrate that both beta-catenin and Lef1 bind directly to the neurogenin promoter, and luciferase reporter assays demonstrate that beta-catenin is directly involved in the regulation of neurogenin 1 and possibly other proneural genes when neural stem cells are cultured in the presence of FGF2." + + + +
+ + + +
+ + + + + + 15031118 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ trips + +
+ +
+
+ + + +
+ + + + + "Elevated beta-catenin levels in colorectal cancer result in the binding of beta-catenin to LEF-1 and increased transcriptional activation of the CCND1 gene." + + + +
+ + + +
+ + + + + + 15557752 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Elevated beta-catenin levels in colorectal cancer result in the binding of beta-catenin to LEF-1 and increased transcriptional activation of the CCND1 gene." + + + +
+ + + +
+ + + + + + 15557752 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "EA Directly Interacts with LEF-1 and Destabilizes the LEF-1 and beta-Catenin Complex." + + + +
+ + + +
+ + + + + + 20011538 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Intermittent PTH is a pathway agonist, thus, the accumulated β-catenin binds to T-cell-specific transcription factor (TCF) and lymphoid enhancing factor (LEF), displacing the Groucho repressor gene, and thereby allowing the transcription of Wnt-specific osteoblast differentiation genes. xref " + + + +
+ + + +
+ + + + + + 28062525 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The binding of unphosphorylated β-catenin to Lef1 in the nucleus to form the transcription activator was modeled using a mass action law (Eq 2.11 in the Additional file xref )." + + + +
+ + + +
+ + + + + + 23602012 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The GSK3-Axin2 degradation complex is in antiphase with the β-catenin-Lef1 transcriptional activator, because it degrades β-catenin and thus inhibits the formation of the β-catenin-Lef1 complex." + + + +
+ + + +
+ + + + + + 23602012 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Research by Juan Galceran et al. [ xref ] confirmed that Lef1 binds to β-catenin in the nucleus to form the Lef1-β-catenin complex that activates the expression of endogenous Dll1 in fibroblasts." + + + +
+ + + +
+ + + + + + 23602012 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Elevated beta-catenin levels in colorectal cancer result in the binding of beta-catenin to LEF-1 and increased transcriptional activation of the CCND1 gene." + + + +
+ + + +
+ + + + + + 15557752 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "It has been demonstrated that LEF-1 is constitutively associated with β-catenin in SW480 cells xref ." + + + +
+ + + +
+ + + + + + 20011538 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "OSTM1 acts also as an E3 ubiquitin ligase for the heterotrimeric G protein Galphai3 and potentiates WNT canonical signaling by modulating beta-catenin and Lef1 interaction." + + + +
+ + + +
+ + + + + + 30837952 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In addition, Wnt signaling activated target gene expression through the interaction of beta-catenin and a LEF-1 and TCF transcription factor family member [XREF_BIBR, XREF_BIBR]." + + + +
+ + + +
+ + + + + + 26580798 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "It has been shown that CK1delta and CK2 phosphorylate Lef-1 [XREF_BIBR] leading to a disruption of interactions between beta-catenin and Lef-1, but not between Lef-1 and the template DNA." + + + +
+ + + +
+ + + + + + 23016862 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "During a high-throughput screening the approved FDA diuretic ethacrynic acid was found to down-regulate Wnt and beta-catenin signaling by inhibiting the formation of the beta-catenin and Lef -1 complex [XREF_BIBR, XREF_BIBR] in chronic lymphocytic leukemia (CLL) cells, although at a low IC 50." + + + +
+ + + +
+ + + + + + 23016862 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Cross-talk with the Wnt pathway is possible at the level of beta-catenin and Lef-1 interactions with EpICD, and known for induction of the EPCAM promoter by Tcf4." + + + +
+ + + +
+ + + + + + 21552419 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Chibby (Cby) inhibits Wnt and beta-catenin-mediated transcriptional activation by competing with Lef-1 (the transcription factor and target of beta-catenin) to bind to beta-catenin." + + + +
+ + + +
+ + + + + + 25175341 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Our research revealed a novel interaction between PITX2, Lef-1, and beta-catenin in which the Lef-1 beta-catenin binding domain is dispensable for its interaction with PITX2." + + + +
+ + + +
+ + + + + + 17785445 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "3D complex structures show that CDH1, LEF1 and TCF7L2 bind to beta-catenin." + + + +
+ + + +
+ + + + + + 27928465 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "LMNADelta9 expressing cells showed a 70% reduction in the nuclear levels of Tcf and Lef1 binding to beta-catenin compared to controls, indicating that Delta9 reduced the levels of active Tcf and Lef-beta-catenin." + + + +
+ + + +
+ + + + + + 20833363 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "These data support a role for PITX2 in cell proliferation, migration, and cell division through differential Lef-1 isoform expression and interactions with Lef-1 and beta-catenin." + + + +
+ + + +
+ + + + + + 17785445 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Cross-talk with the Wnt pathway is possible at the level of β-catenin and Lef-1 interactions with EpICD, and known for induction of the EPCAM promoter by Tcf4." + + + +
+ + + +
+ + + + + + 21552419 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "This approach has been used to inhibit WNT signaling with a β-catenin-ENGR repressor and relies on β-catenin's association with the activator LEF-1, which provides the DNA-binding and promoter targeting function ." + + + +
+ + + +
+ + + + + + 11164187 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Dact proteins have been shown to also modulate Wnt signaling mediators in a ligand independent fashion : Dact proteins shuttle between the nucleus and cytoplasm, and can block nuclear beta-Catenin function by disrupting beta-Catenin and Lef1 complexes and enhancing Lef1-HDAC interaction [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 25099342 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Electrophoretic mobility shift assays (EMSAs) confirmed binding of beta-catenin and Lef1 to the TBE2 site (XREF_FIG)." + + + +
+ + + +
+ + + + + + 24101380 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The ESR1 and beta-catenin conjugation then associated with the transcription factors TCF3 and LEF1." + + + +
+ + + +
+ + + + + + 26432349 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Free beta-catenin interacts with the DNA binding proteins Tcf3 and Lef1 to form a bipartite transactivator that stimulates the transcription of immediate gene targets." + + + +
+ + + +
+ + + + + + 11524435 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In many systems, Lef1 interaction with β-catenin is necessary for Lef1-mediated activation of target genes (reviewed in Behrens et al. 1996; Clevers and van de Wetering, 1997 )." + + + +
+ + + +
+ + + + + + 18280717 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Active beta-catenin binds to LEF1 to form transcription complexes to activate target gene expression." + + + +
+ + + +
+ + + + + + 27441654 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Upon translocation to the nucleus, beta-catenin interacts with Tcf4 and Lef1 to regulate a wide range of gene expression at the transcriptional level [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 20858269 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "10 As a complex, Smad2/3-Smad 4 are then able to enter the nucleus of the epithelial cell and increase transcription of LEF-1, a member of the T-cell family of transcription factors that binds with beta-catenin suppressing transcription of epithelial markers such as E-cadherin and promoting transcription of mesenchymal markers such as vimentin and N-cadherin." + + + +
+ + + +
+ + + + + + 22561306 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "However, it has also been reported that the inhibition of interaction between β-catenin and Lef-1 caused HFSCs to differentiate into sebocytes xref , xref ." + + + +
+ + + +
+ + + + + + 25076848 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The role of beta-catenin in anoikis is also attributable to the activation of the Wnt pathway, in which beta-catenin interacts with transcription factor lymphoid enhancer binding factor 1 (LEF-1) to regulate gene expression and subsequently inhibit anoikis [XREF_BIBR - XREF_BIBR]." + + + +
+ + + +
+ + + + + + 26587543 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In addition, beta-catenin also translocates into the nucleus and interacts with LEF-1 and TCF-4 at the COX2 promoter to activate the transcription of COX2." + + + +
+ + + +
+ + + + + + 28587064 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "However, as β-catenin accumulates in the nucleus, Groucho/TLE is displaced from Tcf/Lef by β-catenin binding to C-terminal of Lef1 (residure252-397)." + + + +
+ + + +
+ + + + + + 20858269 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Lef1 binding site was mapped to the 3 ' region of the MMP13 genomic locus and binding of Lef1 and beta-catenin to the site was confirmed by chromatin immunoprecipitation (ChIP) assays and electrophoretic mobility shift assays (EMSAs)." + + + +
+ + + +
+ + + + + + 17971297 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Furthermore, Lef1 and beta-catenin binding to the Lef1 binding site transactivated MMP13 promoter activity." + + + +
+ + + +
+ + + + + + 17971297 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Upon entering the nucleus, beta-catenin replaces Groucho/TLE, forms complexes with TCF-1 and LEF-1, and activates the transcription of Wnt target genes." + + + +
+ + + +
+ + + + + + 20026746 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In line with our previous findings that DBC1 enhances LEF1-β-catenin complex formation on WREs of β-catenin targets including a Wnt-inducible transcription factor PROX1 involved in colon cancer progression xref , DBC1 increases LEF1-β-catenin interaction on the MACC1 enhancer, and loss of DBC1 reduced the occupancy of LEF1, TCF4, and β-catenin on the MACC1 enhancer." + + + +
+ + + +
+ + + + + + 30082743 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Akt dependent release of FoxO1 and glucose dependent binding of LEF1 and beta-catenin mediate induction of Gip expression while insulin induced phosphorylation of beta-catenin does not alter its localization or transcriptional activity in enteroendocrine cells." + + + +
+ + + +
+ + + + + + 25091498 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "However, unlike embryonic development in which uniform upper dermal Wnt signaling precedes hair morphogenesis ( xref ; xref ; xref ) we could not detect Wnt activity in the upper dermis prior to hair germ formation by either β-catenin or LEF-1 immunohistochemistry or with a Wnt-responsive reporter ( xref , data not shown)." + + + +
+ + + +
+ + + + + + 22810306 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "TGF-beta1 induced nuclear Smad3, beta, and catenin complex, but not beta-catenin and LEF -1 complex or TOP-flash activity, during EMT of C1.1 (renal tubular epithelial) cells." + + + +
+ + + +
+ + + + + + 23203799 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "During hair follicle development in the mouse, epithelial cells of the ectoderm secrete Wnt3a, leading to nuclear accumulation of beta-Catenin, and mesenchymal cells secrete Noggin, which activates the Lef1 transcription factor; Lef1 can subsequently form a heterodimer with beta-Catenin to regulate transcription of target genes XREF_BIBR." + + + +
+ + + +
+ + + + + + 17895986 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Recent biochemical studies indicate that the vertebrate HMG-domain proteins Lef-1 and XTcf-3 can physically interact with beta-catenin, a homologue of Drosophila Armadillo (Arm), the most downstream component known in the Wnt signal transduction pathway." + + + +
+ + + +
+ + + + + + 9039917 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "During gastrulation, beta-catenin forms a complex with LEF-1 to bind and inhibit the transcription of CDH1 (XREF_FIG) and induce EMT." + + + +
+ + + +
+ + + + + + 25249658 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "During gastrulation, β-catenin forms a complex with LEF-1 to bind and inhibit the transcription of CDH1 ( xref ) and induce EMT ( xref )." + + + +
+ + + +
+ + + + + + 25249658 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "beta-Catenin and LEF-1 complexes can activate reporter gene expression in a transformed T-lymphocyte cell line (Jurkat) but not in normal T lymphocytes, even though both factors are nuclear." + + + +
+ + + +
+ + + + + + 10330189 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "This protein inhibits Wnt and beta-catenin mediated transcriptional activation by competing with Lef-1 (the transcription factor and target of beta-catenin) to bind to beta-catenin." + + + +
+ + + +
+ + + + + + 15245581 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Low levels of YREG1 were important for stabilizing the interaction between LEF-1 and beta-catenin, while elevated levels inhibited EMT by downregulating LEF-1 transcriptional activity." + + + +
+ + + +
+ + + + + + 28027307 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "This result suggests that beta-catenin loses its ability to translocate into the nucleus and bind to LEF-1 and TCF-4 following TQ treatment." + + + +
+ + + +
+ + + + + + 28275297 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Transcriptome analysis using gene sets related to the regulation of nuclear beta-catenin signaling and target gene transcription did not reveal a differential expression of the beta-catenin interaction partners LEF1 or TCF7L2 (TCF-4)." + + + +
+ + + +
+ + + + + + 27428425 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "As discussed above, elevated cytosolic β-catenin levels are associated with increased β-catenin nuclear accumulation and LEF-1-mediated transcription, hence the implication is that presenilin-mediated proteolytic cleavage of E-cadherin may contribute to enhanced transcription of genes involved in survival." + + + +
+ + + +
+ + + + + + 12527355 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Also, LEF1 may form complexes with beta-catenin (CTNNB1), T-Cell Factor 4 (TCF7L2), and other proteins (HINT1, RUVBL1) implicated in Wnt / beta-catenin signaling, a crucial developmental pathway [XREF_BIBR - XREF_BIBR]." + + + +
+ + + +
+ + + + + + 28376810 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Surprisingly, however, phosphorylation of murine Ser40 residue (corresponding to human Ser42) by CKIdelta disrupts the beta-catenin and LEF -1 complex [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 24594309 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Wnt and beta-catenin pathway activation is characterized by (i) stabilization of cytoplasmic beta-catenin upon receptor engagement by Wnt ligands, (ii) beta-catenin nuclear translocalion, (iii) beta-catenin interaction with lymphoid enhancer binding factor-1 and T-cell factor-1 (LEF and TCF) transcription factors, and (iv) stimulation of target genes XREF_BIBR, XREF_BIBR." + + + +
+ + + +
+ + + + + + 20852629 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Nuclear β-catenin associates with the Lymphoid Enhancer Factor/T-Cell-Specific Transcription Factor (LEF/TCF) family of transcription factors and activates transcription of Wnt target genes (Reviewed in [ xref ])." + + + +
+ + + +
+ + + + + + 21416313 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Because proinflammatory cytokine induced cartilage degradation appears to involve WNT and beta-catenin signaling and increased WNT and beta-catenin signaling has been implicated in the initiation and progressive deterioration of cartilage degeneration, we hypothesized that small molecule inhibitors of the interaction between beta-catenin and TCF4 and Lef1 could be used to prevent cytokine induced cartilage degradation." + + + +
+ + + +
+ + + + + + 23965253 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In the presence of Wnt, the β-catenin transcriptional co-activator translocates to the nucleus and associates with members of the T-cell factor/ lymphoid enhancer factor (TCF/LEF; hereafter, TCF) family of transcription factors [ xref , xref ]." + + + +
+ + + +
+ + + + + + 30794691 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Subsequently β-catenin interacts with members of the lymphoid enhancer factor 1/T-cell factor (LEF1/TCF) family, resulting in generation of a functional transcription factor complex and the expression of downstream target genes. [ xref ] Non-canonical Wnt ligands bind to FZD family receptors, and ROR2 and RYK co-receptors.[ xref – xref ] This signaling is mainly involved in cytoskeletal reorganization during cancer cell invasion and metastasis.[ xref ][ xref ] At present, five Wnt antagonist families have been described, namely, secreted frizzled-related protein (sFRP), Wnt inhibitory factor 1 (Wif1), Xenopus Cerberus, Wise and Dickkopf (DKK) families.[ xref ]" + + + +
+ + + +
+ + + + + + 19562778 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Further downstream, CK2 is capable of regulating the interaction and transactivation activity of a beta-catenin and LEF -1 complex though phosphorylation of LEF-1 at S42, S61 [XREF_BIBR, XREF_BIBR]." + + + +
+ + + +
+ + + + + + 19387549 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Beta-catenin and LEF -1 complexes target motifs at -75 and -15 within the CCND1 promoter [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 27695879 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "On the other hand, a strong binding of beta-catenin to cadherin, rather than to LEF-1, may result in its cytoplasmic sequestration and the inhibition of transactivation by it." + + + +
+ + + +
+ + + + + + 9628899 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In the canonical Wnt signaling pathway, the beta-catenin in the nucleus forms a complex with LEF1 to activate transcription of the target gene [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 29120400 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The upregulation of the above genes takes place in a direct manner, as we demonstrated, conserved LEF binding sites in MMP-9, 13, 14, ADAMTS-5, and COL10A1 promoters, responsible for their promoter activity and is associated directly with the beta-catenin and LEF -1 complex." + + + +
+ + + +
+ + + + + + 22513174 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Binding of beta-catenin to cadherin, APC protein, and LEF-1 indicates divergent functions of beta-catenin." + + + +
+ + + +
+ + + + + + 9199178 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "TCF1 and LEF1 can bind beta-catenin and activate target genes when the Wnt pathway is active." + + + +
+ + + +
+ + + + + + 24936456 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "103 Similarly, the absence of beta-catenin and LEF1 interaction, via mutations of LEF1 within the N-terminal beta-catenin binding domain, is associated with increased sebaceous cell differentiation and development of sebaceous tumors in humans." + + + +
+ + + +
+ + + + + + 22111711 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "CK1delta and CK2 phosphorylations of LEF1 on S40 in the N-terminal beta-catenin binding domain XREF_BIBR, XREF_BIBR are dispensable for beta-catenin and LEF1 interaction in vitro, 120 and thus their regulatory roles on LEF1 activity remain to be confirmed." + + + +
+ + + +
+ + + + + + 22111711 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In CRC, ILK induces β-catenin–LEF1 interaction and transactivation, the loss of E-cadherin via induction of EMT-TFs, and the induction of stem cell markers xref – xref ." + + + +
+ + + +
+ + + + + + 30271576 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "AEG-1 facilitated β-catenin translocation into the nucleus by forming a complex with LEF1 and β-catenin, subsequently activating Wnt signaling downstream genes." + + + +
+ + + +
+ + + + + + 27903708 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Second, once HDAC1 dependent repression has been overridden, beta-catenin binds LEF1 and the beta, catenin, and LEF1 complex is competent to activate the expression of downstream target genes." + + + +
+ + + +
+ + + + + + 10958684 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ trips + +
+ +
+
+ + + +
+ + + + + "Second, once HDAC1-dependent repression has been overridden, beta-catenin binds LEF1 and the beta-catenin-LEF1 complex is competent to activate the expression of downstream target genes." + + + +
+ + + +
+ + + + + + 10958684 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "However, it has also been reported that the inhibition of interaction between beta-catenin and Lef-1 caused HFSCs to differentiate into sebocytes XREF_BIBR, XREF_BIBR." + + + +
+ + + +
+ + + + + + 25076848 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Surprisingly, beta-catenin directly interacts with the transcription factor LEF-1 and XTCF-3, and thereby is not only translocated into the nucleus but also modulates the properties of LEF-1 and XTCF-3 as a transcription factor." + + + +
+ + + +
+ + + + + + 9046239 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Members of the Lef1 and Tcf family of DNA binding proteins bind beta-catenin and transactivate Wnt target genes XREF_BIBR." + + + +
+ + + +
+ + + + + + 19718027 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "XREF_BIBR - XREF_BIBR Although it is well established that the formation of nuclear beta-catenin and LEF1 complexes has a crucial role in the activation of Wnt target genes, the details of the regulatory mechanisms of beta-catenin activity and its interaction with LEF1 are still under investigation." + + + +
+ + + +
+ + + + + + 26477307 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Furthermore, endogenous interaction between beta-catenin and LEF1 was decreased in DBC1 KO SW480 cells (XREF_FIG), suggesting that DBC1 stabilizes the interaction between beta-catenin and LEF1 by interacting with beta-catenin." + + + +
+ + + +
+ + + + + + 26477307 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Consistent with the model in which beta-catenin acetylation enhances its binding to LEF1 and leads to increased chromatin occupancy of LEF1 by stabilizing LEF1, beta, and catenin complex, XREF_BIBR, XREF_BIBR our results further showed that DBC1 enhances the interaction of beta-catenin with LEF1 (XREF_FIG) and is required for efficient recruitment of LEF1 and beta-catenin to their target chromatin regions (XREF_FIG), probably through protecting beta-catenin from SIRT1 mediated deacetylation (XREF_FIG)." + + + +
+ + + +
+ + + + + + 26477307 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "These results suggest that DBC1 is required for efficient binding of LEF1 to its regulatory regions and/or for stable association of LEF1 with β-catenin, which strongly enhances the binding of LEF1 to chromatin, xref and thereby facilitates the occupancy of p300 and Pol II on the regulatory regions of LEF1–β-catenin target genes." + + + +
+ + + +
+ + + + + + 26477307 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Consistent with these results, DBC1 increased the interaction of β-catenin with LEF1 in vivo and in vitro ( xref )." + + + +
+ + + +
+ + + + + + 26477307 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Furthermore, endogenous interaction between β-catenin and LEF1 was decreased in DBC1 KO SW480 cells ( xref ), suggesting that DBC1 stabilizes the interaction between β-catenin and LEF1 by interacting with β-catenin." + + + +
+ + + +
+ + + + + + 26477307 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Together, these results suggest that DBC1 functions as a positive regulator of β-catenin by inhibiting SIRT1-mediated deacetylation and repression of β-catenin through blocking the interaction between β-catenin and SIRT1, thereby enhancing the association of β-catenin with LEF1 and promoting β-catenin-mediated transcription ( xref )." + + + +
+ + + +
+ + + + + + 26477307 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Consistent with the model in which β-catenin acetylation enhances its binding to LEF1 and leads to increased chromatin occupancy of LEF1 by stabilizing LEF1–β-catenin complex, xref , xref our results further showed that DBC1 enhances the interaction of β-catenin with LEF1 ( xref ) and is required for efficient recruitment of LEF1 and β-catenin to their target chromatin regions ( xref ), probably through protecting β-catenin from SIRT1-mediated deacetylation ( xref )." + + + +
+ + + +
+ + + + + + 26477307 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Upon translocation to the nucleus, beta-catenin interacts with T-cell factor 4 (TCF4) and lymphoid enhancer binding factor 1 (LEF1) to regulate the expression of a wide range of genes at the transcriptional level 12." + + + +
+ + + +
+ + + + + + 28811522 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Protein protein interaction between beta-catenin and Lef-1." + + + +
+ + + +
+ + + + + + 14520463 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Immunoprecipitation was performed in order to detect a physical interaction between beta-catenin, alpha-catenin and Lef-1 (XREF_FIG)." + + + +
+ + + +
+ + + + + + 14520463 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Elevated beta-catenin levels in colorectal cancer caused by mutations in beta-catenin or by the adenomatous polyposis coli molecule, which regulates beta-catenin degradation, result in the binding of beta-catenin to LEF-1 and increased transcriptional activation of mostly unknown target genes." + + + +
+ + + +
+ + + + + + 10318916 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Specificity of the small molecules was demonstrated by coimmunoprecipitation experiments for the lef-1/beta-catenin interaction." + + + +
+ + + +
+ + + + + + 20360943 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Coimmunoprecipitation showed a selective disruption of beta-catenin/lef-1 interaction." + + + +
+ + + +
+ + + + + + 20360943 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Elevated beta-catenin levels in colorectal cancer caused by mutations in beta-catenin or by the adenomatous polyposis coli molecule, which regulates beta-catenin degradation, result in the binding of beta-catenin to LEF-1 and increased transcriptional activation of mostly unknown target genes." + + + +
+ + + +
+ + + + + + 10318916 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Beta-catenin forms a complex with LEF1 and TCFs and transactivates LEF1 and TCF mediated transcriptions during dorsalization." + + + +
+ + + +
+ + + + + + 17404593 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "We observe similar molecular interactions between Lef1 and beta-catenin and vertebrate Hipk2, suggesting a direct and conserved role for Hipk proteins in promoting Wnt signaling." + + + +
+ + + +
+ + + + + + 19088090 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "When beta-catenin binds TCF and Lef1, it can regulate the transcription of Wnt target genes [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 27999816 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Lef1 is a member the Tcf/Lef family of transcription factors and interacts with beta-catenin to up-regulate Wnt target genes." + + + +
+ + + +
+ + + + + + 30872674 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Specificity of the small molecules was demonstrated by coimmunoprecipitation experiments for the lef-1 and beta-catenin interaction." + + + +
+ + + +
+ + + + + + 20360943 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Coimmunoprecipitation showed a selective disruption of beta-catenin and lef -1 interaction." + + + +
+ + + +
+ + + + + + 20360943 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "After nuclear translocation, beta-catenin binds to DNA binding proteins Tcf and Lef1 which subsequently regulates target genes including Cyclin D1 [XREF_BIBR] important in proliferation." + + + +
+ + + +
+ + + + + + 27750091 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Recent studies indicate that increased levels of beta-catenin correlate with the downregulation of the Wnt and beta-catenin pathway due to the proteasomal degradation of beta-catenin and the subsequent decrease in cyclin D [XREF_BIBR], as the cyclin D1 gene might be a target of the beta-catenin and LEF -1 complex [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 23970935 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Nuclear β-catenin binds to LEF1, displacing the Groucho/TLE repressors, resulting in transcriptional activation of downstream target genes (c-MYC, Cyclin D1, and LEF1) in response to activation of canonical WNT signaling [ xref ]." + + + +
+ + + +
+ + + + + + 29535816 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Nuclear beta-catenin binds to LEF1, displacing the Groucho/TLE repressors, resulting in transcriptional activation of downstream target genes (c-MYC, Cyclin D1, and LEF1) in response to activation of canonical WNT signaling [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 29535816 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Proteolysis of EpCAM leads EpICD to form complex withFHL2, β-catenin and Lef1." + + + +
+ + + +
+ + + + + + 26176230 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "To directly assay for binding of LEF-1 and β-catenin to these sites, electrophoretic gel-mobility shift analysis was performed with recombinant LEF-1 and β-catenin produced in ()." + + + +
+ + + +
+ + + + + + 10704849 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Accordingly, ectopic LEF1 expression increases β-catenin binding to TCF-binding sequences and activates the MMP7 promoter [ xref ]." + + + +
+ + + +
+ + + + + + 28757546 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "β-Catenin in the nucleus interacts with transcription factor T-cell factor (TCF) and/or lymphoid enhancer factor (LEF), promoting expression of specific genes." + + + +
+ + + +
+ + + + + + 26109834 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Interaction between beta-catenin and LEF-1 was assessed in vivo in C3H10T1/2 SS18-SSX-V5 and C3H10T1/2 pLIVc cells by proximity ligation assay (PLA), using a polyclonal goat anti-LEF-1 and a mouse anti-beta-catenin antibody." + + + +
+ + + +
+ + + + + + 26905812 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Wnt3a stimulation of C3H10T1/2 pLIVc (0.1 muM for 16h) did not result in significant dissociation of HDAC from LEF-1 (not shown) whereas it increased association between LEF-1 and beta-catenin, as discussed earlier (XREF_FIG)." + + + +
+ + + +
+ + + + + + 26905812 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Moreover, when the endogenous Smad7 was repressed by specific small interfering RNA, TGF-beta-induced increase of activated p38, Akt phosphorylated on Ser473, glycogen synthase kinase 3beta phosphorylated on Ser9 was prevented, as well as the TGF-beta-induced association between beta-catenin and LEF1." + + + +
+ + + +
+ + + + + + 15684397 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Interaction between β-catenin and LEF-1 was assessed in vivo in C3H10T1/2 SS18-SSX-V5 and C3H10T1/2 pLIVc cells by proximity ligation assay (PLA), using a polyclonal goat anti-LEF-1 and a mouse anti-β-catenin antibody." + + + +
+ + + +
+ + + + + + 26905812 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "HQ blocked nuclear translocation of β-catenin and lymphoid enhancer-binding factor 1 (LEF-1), and importantly, HQ also reduced the interaction of β-catenin and LEF-1 in the nucleus." + + + +
+ + + +
+ + + + + + 28886972 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "To determine whether the in silico identified LEF-1 and TCF binding sequences physically bind to the beta-catenin and Lef -1 complex in vitro, we conducted a competitive electrophoretic mobility-shift assay (EMSA) with a radioactively labeled consensus LEF-1 and TCF strong binding probe and duplex oligonucleotides covering the potential sites in target promoters." + + + +
+ + + +
+ + + + + + 21437251 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Hes-1 has recently also been identified as a direct transcriptional target of beta-catenin and Tcf-4-dependent Wnt signaling in CRC XREF_BIBR and our EMSA data supports this notion by clearly identifying Hes-1 -528 as a binding site for the beta-catenin and Lef -1 complex (XREF_SUPPLEMENTARY)." + + + +
+ + + +
+ + + + + + 21437251 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In this study, we show that the beta-catenin and Lef -1 complex is capable of binding to the Jagged-1 promoter in vitro at positions -1933, -1635 and possibly -1083 relative to the translation start site (XREF_FIG and XREF_SUPPLEMENTARY) making these plausible sites for transcriptional interactions between Jagged-1 and the canonical Wnt pathway." + + + +
+ + + +
+ + + + + + 21437251 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "HQ blocked nuclear translocation of beta-catenin and lymphoid enhancer binding factor 1 (LEF-1), and importantly, HQ also reduced the interaction of beta-catenin and LEF-1 in the nucleus." + + + +
+ + + +
+ + + + + + 28886972 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Taken together, our results suggest that HQ induced hematotoxicity in bone marrow mononuclear cells is associated with dysregulation of Akt/GSK-3beta/beta-catenin signaling due to the dissociation of beta-catenin and LEF -1 complex, and LiCl and IGF-1 may be two potential agents to ameliorate HQ induced hematotoxicity." + + + +
+ + + +
+ + + + + + 28886972 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In this scenario, tumor cells with activated EpCAM i.e. the released EpICD associates with FHL2, β-catenin which form a nuclear complex with Lef-1 and induces transcription of genes associated with cell proliferation. (Figure xref ; Schematic diagram modified from Maetzel D et al., 2009) [ xref ]." + + + +
+ + + +
+ + + + + + 28903370 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The expressed LEF1 then associates with beta-catenin to drive further expression of full-length LEF1 [ xref ]." + + + +
+ + + +
+ + + + + + 26509276 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Moreover, CK1-dependent phosphorylation in contrast to CK2 disrupts the association of beta-catenin and LEF-1 but does not impair DNA binding of LEF-1." + + + +
+ + + +
+ + + + + + 15747065 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Moreover, β-catenin, a protein found at cell–cell adherens junctions, has been shown to play a role in both linking the actin cytoskeleton to the cadherin class of homophilic cell adhesion receptors as well as directly transducing Wnt/ Wingless signals ( xref ; xref ; xref ); Wnt/Wingless signaling results in the nuclear accumulation of a β-catenin-Lef-1 transcription factor complex that binds the promoter regions of several genes (Behrens, et al., 1996; Huber, et al., 1996 b )." + + + +
+ + + +
+ + + + + + 9281590 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Transcription factor LEF-1, which acts as a dimer, binds beta-catenin and is involved in signal transduction by the wnt pathway." + + + +
+ + + +
+ + + + + + 11440173 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "TCF1, LEF1 and TCF4 can bind beta-catenin and activate transcription of target genes as a result of Wnt signaling." + + + +
+ + + +
+ + + + + + 29443926 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In colon cancer cells, beta-catenin and LEF1 complexes drive transcription of the full-length LEF1 isoform that can bind beta-catenin at the expense of a dominant negative isoform." + + + +
+ + + +
+ + + + + + 26509276 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The expressed LEF1 then associates with beta-catenin to drive further expression of full-length LEF1 [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 26509276 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In the present study, we explored the mechanism (s) through which NO exerts its effect on cytosolic beta-catenin accumulation and nuclear beta-catenin and LEF -1 complex formation." + + + +
+ + + +
+ + + + + + 12507936 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Furthermore, the degradation of E-cadherin and the release of beta-catenin to cytosol were accompanied by the formation of nuclear beta-catenin and LEF -1 complex, demonstrating the dissociation of beta-catenin from E-cadherin may be responsible for the activation of beta-catenin and LEF -1 transcription complex." + + + +
+ + + +
+ + + + + + 12507936 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "These MMP inhibitors also blocked the cytosolic accumulation of beta-catenin and nuclear formation of beta-catenin and LEF -1 complex." + + + +
+ + + +
+ + + + + + 12507936 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The sum effect of MMP inhibitors demonstrated that NO induced activation of MMP may cause the degradation of E-cadherin and the subsequent dissociation of beta-catenin, thereby contributing to the cytosolic accumulation of beta-catenin and nuclear formation of beta-catenin and LEF -1 complex." + + + +
+ + + +
+ + + + + + 12507936 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "One possible explanation is that over-inhibition of GSK3 increases the expression of the canonical Wnt pathway effector LEF1, and elevated LEF1 interacts with beta-catenin and leads to activation of lineage specification genes Cdx2 and T [XREF_BIBR] (XREF_FIG)." + + + +
+ + + +
+ + + + + + 25595304 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "41 + In sharp contrast, smad4, another effector of TGF-β, has been shown to form a complex with β-catenin and LEF-1 and to increase β-catenin/LEF-1 transcriptional activity in a hepatoma cell line." + + + +
+ + + +
+ + + + + + 11839557 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Mechanistically, TCF4 and LEF1 forms a complex with beta-catenin to bind its target gene promoters and promote cancer cell proliferation 28." + + + +
+ + + +
+ + + + + + 29765046 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "What is the structural basis of specific protein-protein interactions, such as those between homeodomain proteins and β-catenin-Lef1 interactions, and how are these determinants altered in transcriptional regulation in oncogenesis and in genetic diseases?" + + + +
+ + + +
+ + + + + + 10456033 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "As mentioned above, their second selected target, Lef-1, binds nuclear β-catenin in Wnt signaling (section 3.2)." + + + +
+ + + +
+ + + + + + 23531534 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "Activated dvl binds and inhibits the phosphorylation of beta catenin by gsk3beta/alfa, blocking beta catenin degradation), so that beta catenin accumulates and translocates to the nucleus, where it interacts with the t cell specific factor (tcf)/lymphoid enhancer binding factor 1 (lef-1) transcription factor and induces the transcription of target genes such as c-jun, c-myc, and cyclin d1" + + + +
+ + + +
+ + + + + + 15735151 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Active Wnt/β-catenin signalling induces the stabilization of cytosolic β-catenin, which then associates with lymphoid enhancer factor and T-cell factor, such as transcription factor 7-like 2 (TCF7L2 or TCF4) to form a transcription complex that activates Wnt target genes." + + + +
+ + + +
+ + + + + + 22767436 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "To confirm that the compounds inhibit LEF-1 and beta-catenin DNA binding, EMSA assays were performed with immunoprecipitated beta-catenin and a 32 P labeled double stranded deoxyoligonucleotide (5 '-CCCTTTGATCTTACC-3 ') containing the LEF-1 consensus binding site in the presence of varied concentrations of the compounds." + + + +
+ + + +
+ + + + + + 19216569 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "A high proportion of human sebaceous adenomas have amino acid substitutions in the N-terminus of Lef1, which impair the binding of Lef1 to beta-catenin resulting in the inhibition of beta-catenin-dependent transcription of Wnt target genes [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 22960253 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "LEF-1 transcription factors are regarded to be the most downstream effectors in the wnt-signalling regulation pathway, forming a complex with β-catenin before binding DNA." + + + +
+ + + +
+ + + + + + 10433970 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Whereas it is recognized that beta-catenin and LEF1 interaction is important in the earlier development of tooth formation, the observed decrease in expression may be associated with the function of Lef1 in the regulation of Enam expression." + + + +
+ + + +
+ + + + + + 22243241 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "A high proportion of human sebaceous adenomas have amino acid substitutions in the N-terminus of Lef1, which impair the binding of Lef1 to β-catenin resulting in the inhibition of β-catenin-dependent transcription of Wnt target genes [ xref ]." + + + +
+ + + +
+ + + + + + 22960253 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Nuclear beta-catenin binds to TCF and Lef1 to induce transcriptional activity, which is a hallmark of Wnt and beta-catenin signaling activation." + + + +
+ + + +
+ + + + + + 26663639 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "Upon wnt activation, cytoplasmic beta-catenin is stabilized and enters the nucleus, where it associates with transcription factors, notably tcf (t cell factor) and lef (lymphoid enhancer-binding factor), to regulate the transcription of target genes. Thus beta-catenin regulates gene expression by direct interaction with transcription factors such as lef-1, providing a molecular mechanism for the transmission of signals, from cell-adhesion components or wnt protein to the nucleus." + + + +
+ + + +
+ + + + + + 23151663 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "Phosphorylated lrp5/6 leads to inhibition of the so-called beta-catenin destruction complex (which includes axin, gsk3, dvl, ck1, and the tumor suppressor adenomatous polyposis coli), resulting in the stabilization and translocation of beta-catenin in the nucleus, where it activates target genes through binding to tcf/lef transcription factors." + + + +
+ + + +
+ + + + + + 21078818 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds LEF1 and PITX2. + + 14 / 14 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 14 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The canonical Wnt signaling pathway is one mechanism where β-catenin and Lef-1 can independently interact with PITX2 to increase its transcriptional activity ( xref , xref )." + + + +
+ + + +
+ + + + + + 18045789 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Because PITX2 interacts with β-catenin and Lef-1 to regulate gene expression we asked if Dact2 interacted with PITX2 to modulate PITX2 transcriptional activity." + + + +
+ + + +
+ + + + + + 23349981 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Pitx2, Lef-1 and β-catenin are associated as a complex when activating downstream gene expression xref ." + + + +
+ + + +
+ + + + + + 23349981 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "It was previously shown that Dact2 inhibits Lef-1 interaction with β-catenin, however, Dact2 does not appear to inhibit the interaction of Pitx2 with β-catenin or Lef-1, but modulates their synergistic transcriptional activities." + + + +
+ + + +
+ + + + + + 23349981 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "This regulation of gene expression appears to be linked with Wnt/β-catenin signaling through β-catenin interactions with Lef-1 and Pitx2." + + + +
+ + + +
+ + + + + + 23349981 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Expression of Lef1 is regulated through direct physical interactions of PITX2, LEF1 and β-catenin ( xref ), and PITX2 enhances endogenous expression of the full-length β-catenin-dependent Lef1 isoform while decreasing expression of the N-terminally truncated β-catenin-independent isoform ( xref )." + + + +
+ + + +
+ + + + + + 20200414 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Our research revealed a novel interaction between PITX2, Lef-1, and beta-catenin in which the Lef-1 beta-catenin binding domain is dispensable for its interaction with PITX2." + + + +
+ + + +
+ + + + + + 17785445 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Lef-1 and beta-catenin interact simultaneously and independently with PITX2 through two different sites to regulate PITX2 transcriptional activity." + + + +
+ + + +
+ + + + + + 17785445 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "LEF-1 and β-catenin bind Pitx2 promoter sequences in ocular neural crest, indicating a likely direct effect of canonical Wnt signaling on Pitx2 expression." + + + +
+ + + +
+ + + + + + 20960542 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In this report, we present evidence that canonical Wnt/ β-catenin signaling is not required for initial activation of Pitx2 , but it is required for maintenance of its continued expression likely via direct binding of Lef-1 and β-catenin to the Pitx2 promoter." + + + +
+ + + +
+ + + + + + 20960542 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Β-catenin and LEF1 bind Pitx2 promoter sequences in developing periocular mesenchyme." + + + +
+ + + +
+ + + + + + 20960542 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Furthermore, beta-catenin in combination with PITX2 synergistically activates the LEF-1 promoter and this activation is independent of the Wnt-responsive element. beta-catenin directly interacts with PITX2 to synergistically regulate LEF-1 expression." + + + +
+ + + +
+ + + + + + 15728254 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We show a new mechanism where LEF-1 expression is regulated through PITX2, LEF-1 and beta-catenin direct physical interactions." + + + +
+ + + +
+ + + + + + 15728254 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "LEF-1 and beta-catenin interactions with PITX2 provide new mechanisms for the regulation of PITX2 transcriptional activity." + + + +
+ + + +
+ + + + + + 15728254 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ TCF4 binds LEF1 and CTNNB1. + + 12 / 12 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 12 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In addition, the interaction between β-catenin with TCF4 or LEF1 was also enhanced in mPGES-1 overexpressed cells but decreased in mPGES-1 knockdown cells." + + + +
+ + + +
+ + + + + + 21743491 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We observed that in both cases β-CATENIN protein–protein interactions with either LEF-1 or TCF-4 were dramatically decreased after ICG-001 treatment." + + + +
+ + + +
+ + + + + + 23307470 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Our Chromatin immunoprecipitation assay demonstrated a strong binding of β-catenin to the TCF-4 and LEF-1 sites located around -703 and -685 regions of the PDGF-B gene promoter in the KPA cancer cells, while no significant binding was found in the KPC cancer cells (Figure xref D)." + + + +
+ + + +
+ + + + + + 30809277 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Here, we present ITC measurements of Lef-1 and Tcf4 binding to β-catenin under identical conditions, which show that Lef-1 binds slightly less strongly than Tcf4 to β-catenin." + + + +
+ + + +
+ + + + + + 21075118 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Given the difference in the structures of TCF-4 and Lef-1 bound to β-catenin, it was of interest to compare the thermodynamics of these complexes." + + + +
+ + + +
+ + + + + + 21075118 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Β-catenin binds TCF-4 or LEF-1 to regulate cognate gene expression." + + + +
+ + + +
+ + + + + + 21744004 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In addition, β-catenin also translocates into the nucleus and interacts with LEF-1 and TCF-4 at the COX2 promoter to activate the transcription of COX2." + + + +
+ + + +
+ + + + + + 28587064 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Upon translocation to the nucleus, β-catenin interacts with Tcf4 and Lef1 to regulate a wide range of gene expression at the transcriptional level [ xref ]." + + + +
+ + + +
+ + + + + + 20858269 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Because proinflammatory cytokine-induced cartilage degradation appears to involve WNT/β-catenin signaling and increased WNT/β-catenin signaling has been implicated in the initiation and progressive deterioration of cartilage degeneration, we hypothesized that small molecule inhibitors of the interaction between β-catenin and TCF4 and Lef1 could be used to prevent cytokine-induced cartilage degradation." + + + +
+ + + +
+ + + + + + 23965253 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In addition, CGP049090, which blocks the binding of β-catenin to TCF4 and Lef1 [ xref ], was not as effective as PKF115-584." + + + +
+ + + +
+ + + + + + 23965253 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Similarly, the interaction between nuclear β-catenin and TCF-4 or LEF-1 was reduced by CaSR activation ( Fig. 6D ), indicating an inhibitory association of β-catenin and TCF-4 or LEF-1 in the nucleus." + + + +
+ + + +
+ + + + + + 27108064 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "APC mutations and β- catenin gene mutations increase the association of β-catenin with the TCF-4 and Lef-1, xref xref which are involved in the transcriptional regulation of E-cadherin xref and possibly, of other target genes and provide evidence of functional interaction between signaling pathways and cell adhesion molecules during tumorigenesis." + + + +
+ + + +
+ + + + + + 21772890 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Wnt binds CTNNB1 and LEF1. + + 12 / 12 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 12 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Moreover, treatment with the Rac1 inhibitor NSC23766 resulted in a marked reduction in interactions between β-catenin and LEF-1 in the nuclei of Wnt-treated cells ( xref B)." + + + +
+ + + +
+ + + + + + 26403202 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Therefore, we want to know whether CHIP influences the interaction between LEF1 and β-catenin which then promotes Wnt signaling cascade." + + + +
+ + + +
+ + + + + + 33431799 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Nuclear RAC1 in complex with β-catenin facilitates RAC1-dependent phosphorylation of β-catenin on serines 161 and 605, resulting in the formation of nuclear β-catenin-LEF-1, which is necessary for the transactivation of Wnt-dependent genes [ xref ]." + + + +
+ + + +
+ + + + + + 35013128 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "After accumulation, activated β-catenin translocates into the nucleus and forms a complex with the transcriptional factor T-cell factor/ lymphoid enhancer-binding factor 1 (TCF/LEF1) to initiate transcription of Wnt target genes [ xref ]." + + + +
+ + + +
+ + + + + + 28417011 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In the presence of Wnt signaling, the accumulated β-catenin in cytoplasm and nucleus interacts with LEF1." + + + +
+ + + +
+ + + + + + 19000719 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "β-Catenin can then interact with members of the lymphoid enhancer factor/T-cell factor (LEF/TCF) family of architectural transcription factors in the nucleus, inducing transcription of Wnt-responsive genes (for reviews see xref ; xref )." + + + +
+ + + +
+ + + + + + 10893270 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In response to Wnt signals, β-catenin is stabilized and interacts with the N-terminus of Lef-1 to activate transcription of Wnt-responsive genes ( xref – xref )." + + + +
+ + + +
+ + + + + + 17068080 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Upon translocation to the nucleus, β-catenin forms a complex with transcription factors T-cell specific transcription factor (TCF) and Lymphoid enhancer binding factor (LEF) to drive transcription of key Wnt target genes including Axin2 and Nkd1 ." + + + +
+ + + +
+ + + + + + 27083283 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In the canonical Wnt signaling pathway, the β-catenin in the nucleus forms a complex with LEF1 to activate transcription of the target gene [ xref ]." + + + +
+ + + +
+ + + + + + 29120400 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In the absence of Wnt ligand binding, cytoplasmic β-catenin is degraded by the ubiquitin-proteosome pathway and prevented from entering the nucleus and associating with Lef1 to activate Wnt target genes +[ xref , xref ]." + + + +
+ + + +
+ + + + + + 24405829 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In turn, the released EpICD associates with components of the Wnt pathway, β-catenin and LEF-1, and regulates gene transcription, inducing proliferation and tumorigenesis in mice." + + + +
+ + + +
+ + + + + + 20851183 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In the canonical Wnt pathway, β-catenin that migrates to the nucleus interacts with two transcription factors, T-cell-transcription factor (TCF) and lymphoid-enhancer-binding factor 1 (LEF-1), to induce the expression of genes that are crucial in the G1–S-phase transition, such as cyclin D1 and c-myc ." + + + +
+ + + +
+ + + + + + 12767722 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds LEF1 and TCF_LEF. + + 9 / 9 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 9 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Buscarlet and colleagues demonstrated that active β-catenin binds to TCF/Lef at a site on Lef-1, where it displaces Groucho/TLE, which overlaps with the Lef-1-binding site. xref Other reports have shown that the modification of TLE by XIAP-mediated ubiquitylation decreases its affinity with β-catenin, thereby allowing the formation of the β-catenin/TCF complex and thus the switch to an activated Wnt signaling pathway. xref The molecular mechanism by which NDRG1 functions in ESCC remains unclear." + + + +
+ + + +
+ + + + + + 27414086 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Nuclear CTNNB1 binds the transcription factors LEF1 (lymphoid enhancer-binding factor 1) and TCF (T-cell factor), thereby converting LEF1 into a transcriptional activator ( xref )." + + + +
+ + + +
+ + + + + + 23442321 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "This allows the formation of complexes of β-catenin with TCF or LEF1, two closely related transcription factors, which then translocate into the nucleus and regulate target gene transcription in response to Wnt ligands." + + + +
+ + + +
+ + + + + + 19153598 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The β-catenin proteins then translocate to the nucleus via BCL9 and Pygo1 [ xref ] where β-catenin interacts with the T-cell factor (TCF) and lymphoid enhancer factor (LEF) transcriptional activators resulting in upregulation of TCF/LEF target genes." + + + +
+ + + +
+ + + + + + 32560059 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "As a TF, β-catenin assembles with the DNA-binding proteins TCF and LEF-1 to activate genes that drive cell proliferation." + + + +
+ + + +
+ + + + + + 27050516 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The inactivation of GSK-3β and the subsequent stability and nuclear translocation of β-catenin and formation of a Lef1–Tcf–β-catenin complex plays a fundamental role for the differentiation of the HM cells into the precortical HM and HS ( xref ; xref )." + + + +
+ + + +
+ + + + + + 17485490 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In NLK-knockout cells, there is a constitutive interaction between Lef1 and β-catenin, which could explain the elevated Tcf/Lef promoter activity in these cells." + + + +
+ + + +
+ + + + + + 27903773 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Β-catenin forms complexes with Tcf and Lef-1 and functions as a transcriptional activator in the Wnt signalling pathway." + + + +
+ + + +
+ + + + + + 11437403 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "When the Wnt signaling pathway is activated, β-catenin interacts with the TCF and lymphoid enhancer–binding factor (LEF) in the nucleus." + + + +
+ + + +
+ + + + + + 27910912 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ LEF1 binds CTNNB1 and FHL2. + + 9 / 9 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 9 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Consistent with this prediction, we could show the formation of an FHL2β-cateninLEF-1 ternary protein complex in a GST pull-down assay with bacterially expressed GST–FHL2 and in vitro–translated myc–β-catenin and HA–LEF-1 ( xref , lane 8)." + + + +
+ + + +
+ + + + + + 12370240 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Furthermore, β-catenin is able to bind simultaneously to FHL2 and the transcription factor LEF-1, forming a ternary protein complex." + + + +
+ + + +
+ + + + + + 12370240 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Following RIP, the EpICD fragment is translocated from the cytoplasm into the nucleus and form complex with FHL2, beta-catenin, and Lef-1, stimulating the expression of c-Myc and cyclin A/E genes [ xref ]." + + + +
+ + + +
+ + + + + + 32046162 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "EpICD binds to DNA in a complex with the scaffolding protein FHL2, β-catenin, and Lef-1, and regulates cell proliferation ( xref )." + + + +
+ + + +
+ + + + + + 21464043 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Maetzel et al ( xref ) revealed that knockdown of EpCAM in FaDu cells results in decreased proliferation, and they concluded that the proliferative action of EpCAM was attributed to the ability of EpICD to form a transcription activator complex with four and a half LIM domains 2, β-Catenin and lymphoid enhancer binding factor 1 (LEF1) ( xref )." + + + +
+ + + +
+ + + + + + 30015855 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Released EpICD forms a nuclear complex with FHL2, Lef-1 and β-catenin, activating the downstream signal transduction pathway []." + + + +
+ + + +
+ + + + + + 29981429 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Released EpICD associates with FHL2, β-catenin and Lef-1 to form a nuclear complex and triggers oncogenic signaling." + + + +
+ + + +
+ + + + + + 27176150 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "By inhibiting the cleavage of EpCAM, EpAb2-6 prohibits tumor growth by preventing the translocation of EpICD into the nucleus (Fig. xref ), thus preventing the binding of EpICD to a multiprotein complex consisting of FHL2, β-catenin, and Lef-1, and thereby blocking both the down-regulation of p53 and p21, and the activation of EMT and iPS genes." + + + +
+ + + +
+ + + + + + 26317650 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The released EpICD forms nuclear protein complex by interacting with the FHL2, β-catenin and Lef1 mediates gene transcriptions and aids in cell proliferation." + + + +
+ + + +
+ + + + + + 26176230 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ LEF1 binds HNF1A and CTNNB1. + + 7 / 7 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 7 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Activation of β-catenin can also induce the expression of differentiation genes and the induction of these genes in ESCs depends on the interaction of β-catenin with LEF1 and TCF1, two of the four LEF1/TCF family members ( xref ; xref )." + + + +
+ + + +
+ + + + + + 28288968 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Furthermore, overexpression of ICAT, which blocks the binding of β-catenin to TCF-1 and LEF-1, is known to result in a thymocyte development block at the DN to DP transition step in FTOC assays ( xref ), suggesting an essential role for β-catenin/TCF-1 in the DN to DP transition." + + + +
+ + + +
+ + + + + + 22535304 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Both TCF1 and LEF1 interact with β-catenin to regulate the DP (CD4 + CD8 + ) cell differentiation into CD4 + T cells, and in this process, Th-POK is an upstream regulator." + + + +
+ + + +
+ + + + + + 31684152 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "For instance, when ICAT, the inhibitor of β-catenin and TCF, which blocks the binding of β-catenin to TCF-1 and LEF-1, was over-expressed through retroviral transduction, thymocyte development was blocked at the DN to DP transition in FTOC assays, xref indicating an essential role for β-catenin/TCF-1 in the DN to DP transition during thymocyte development." + + + +
+ + + +
+ + + + + + 22321106 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "However, activation of Ctnnb1 can also induce the expression of differentiation genes, such as , and , and the induction of these genes in mESCs mainly depends on the interactions of CTNNB1 with LEF1 and TCF1 (; ; )." + + + +
+ + + +
+ + + + + + 28943339 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "TCF1 and LEF1 can bind β-catenin and activate target genes when the Wnt pathway is active ( xref )." + + + +
+ + + +
+ + + + + + 24936456 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Studies in vertebrates and Drosophila have led to a model in which Wnt signaling regulates an interaction between beta-catenin and POP-1-related proteins such as Tcf-1 or Lef-1." + + + +
+ + + +
+ + + + + + 9458047 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ WNT3A binds CTNNB1 and LEF1. + + 5 / 5 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 5 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The ubiquitinated LEF1 accelerates the interaction between β-catenin and LEF1, which is further heightened after Wnt3a treatment." + + + +
+ + + +
+ + + + + + 33431799 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We compared the ability of OSTM1 and OSTM1ΔC to regulate the Wnt3a-induced binding of β-catenin to Lef1 ( Fig. 6 )." + + + +
+ + + +
+ + + + + + 18296023 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Β-catenin binding to Lef1 increased in cells treated with Wnt3a ( Fig. 6 , compare lanes 1 and 2)." + + + +
+ + + +
+ + + + + + 18296023 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Overexpression of OSTM1 intensified, while OSTM1ΔC inhibited, the Wnt3a-stimulated interaction of β-catenin with Lef1, suggesting that OSTM1 may function as a mediator of this critical protein complex." + + + +
+ + + +
+ + + + + + 18296023 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Norcantharidin reduces 80% of Wnt3a-induced β-catenin binding with lymphoid enhancer factor/T-cell factor protein [ xref ]." + + + +
+ + + +
+ + + + + + 26369691 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds SIRT1 and LEF1. + + 4 / 4 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 4 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Strikingly, LiCl disrupted the SIRT1/LEF-1 complexes induced by glucose, most likely owing to competition for LEF-1 binding between β-catenin (accumulated by LiCl) and SIRT1." + + + +
+ + + +
+ + + + + + 23273980 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Collectively, the results indicate that combined glucose and LiCl treatment increases p300-LEF-1-β-catenin interaction while preventing SIRT1-LEF-1 and SIRT1-β-catenin interaction and suggest that increased acetylation by p300 may be required for nuclear retention of the LEF-1/β-catenin complex." + + + +
+ + + +
+ + + + + + 23273980 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Interestingly, SIRT1 interaction with both β-catenin and LEF-1 is increased in response to high glucose, but these complexes are disrupted in the presence of LiCl." + + + +
+ + + +
+ + + + + + 23273980 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Mechanistically, DBC1 stabilizes LEF1–β-catenin interaction by inhibiting SIRT1-mediated β-catenin deacetylation, thereby enhancing LEF1–β-catenin complex formation and long-range chromatin looping at the PROX1 locus." + + + +
+ + + +
+ + + + + + 26477307 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ KLF10 binds LEF1 and CTNNB1. + + 3 / 3 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 3 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The C-terminal TIEG1 expression construct primarily interacted with Lef1 and β-catenin in the nucleus (Figure xref )." + + + +
+ + + +
+ + + + + + 28201653 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In addition to modulating β-catenin nuclear localization, we also reveal that TIEG1 interacts with Lef1 and β-catenin on Tcf/Lef enhancer elements resulting in enhancement of the canonical Wnt signaling pathway in osteoblasts." + + + +
+ + + +
+ + + + + + 28201653 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We also demonstrated that TIEG1 interacts with both Lef1 and β-catenin proteins suggesting that it associates with these factors as part of a larger transcriptional complex on Tcf/Lef enhancer elements encoded within classic canonical Wnt target genes." + + + +
+ + + +
+ + + + + + 28201653 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ LEF1 binds CTNNB1 and NCAPD2. + + 3 / 3 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 3 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The results are consistent with the general pathway in which Lef-1 forms a bipartite transcriptional activation complex with β-catenin ( Behrens et al., 1996; Willert and Nusse, 1998 )." + + + +
+ + + +
+ + + + + + 12039047 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We also show that complementary charged and hydrophobic amino acids are required for formation of the bipartite beta-catenin-LEF-1 transcription factor." + + + +
+ + + +
+ + + + + + 10966653 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Overexpression or constitutive activation of ILK has been shown to result in an invasive phenotype concomitant with downregulation of E-cadherin expression, translocation of β-catenin to the nucleus, and formation of the LEF-1–β-catenin bipartite complex ( xref ; xref )." + + + +
+ + + +
+ + + + + + 11402061 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds TCF7L2 and LEF1. + + 2 / 2 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 2 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Upon translocation to the nucleus, β-catenin interacts with T-cell factor 4 (TCF4) and lymphoid enhancer-binding factor 1 (LEF1) to regulate the expression of a wide range of genes at the transcriptional level xref ." + + + +
+ + + +
+ + + + + + 28811522 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The nuclear β-catenin may bind in a complex with the T-cell factor 4 (Tcf4) to the Tcf4/ lymphoid enhancer factor (LEF) binding motif at the MDR1 promoter and thus enhancing promoter activity leading to increased efflux of anticancer drugs of the cell [ xref ]." + + + +
+ + + +
+ + + + + + 29409484 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds LEF1 and GSK3B. + + 2 / 2 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 2 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "CHIP influences the interactions between β-catenin and LEF1 or GSK3β, as well as GSK3β and Arc." + + + +
+ + + +
+ + + + + + 33431799 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Taken together, CHIP acts as a cargo to regulate Wnt signaling and the degradation of Arc by influencing the interactions between β-catenin and LEF1 or GSK3β, as well as GSK3β and Arc." + + + +
+ + + +
+ + + + + + 33431799 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ RUNX2 binds CTNNB1 and LEF1. + + 2 / 2 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 2 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Menin is considered to support BMP-2- and Runx2-induced differentiation of mesenchymal cells into osteoblasts by interacting with Smad1/5, Runx2, β-catenin and LEF-1, although it has different effects on osteoblasts at later differentiation stages through TGF-β-Smad3 and AP-1 pathways." + + + +
+ + + +
+ + + + + + 22543820 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Conversely, a ternary complex composed of β-catenin::LEF1::Runx2 was found to inhibit Runx2 from binding to DNA in mouse osteoblast cells ( xref )." + + + +
+ + + +
+ + + + + + 31740621 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds TCF7 and LEF1. + + 2 / 2 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 2 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We did observe strong binding of β-catenin, Tcf7 and Lef1 near Axin2 promoter and a distal site 30 kb upstream in high CHIR condition only." + + + +
+ + + +
+ + + + + + 33587034 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Β-catenin bound the transcription factors Tcf7 and Lef1, which promoted transcription of targeted genes, as evidenced by the increased gene expression of Jun , Fzd7 , and Nlk after TWS119 treatment." + + + +
+ + + +
+ + + + + + 31119051 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ MTDH binds LEF1 and CTNNB1. + + 2 / 2 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 2 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "AEG-1 forms a complex with LEF1 and β-catenin, and AEG-1-mediated activation of the Wnt/β-catenin pathway facilitated the maintenance of glioma stem-like cells and their self-renewal [ xref ]." + + + +
+ + + +
+ + + + + + | PMC + + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We showed that AEG-1 forms a complex with LEF1 and β-catenin, and AEG-1-mediated activation of Wnt/β-catenin pathway facilitated maintenance of glioma stem-like cells and their self-renewal ( xref )." + + + +
+ + + +
+ + + + + + 34353442 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ LEF1 binds CTNNB1 and TLE1. + + 2 / 2 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 2 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The observation that β-catenin and CK2 alternate with TLE1 for binding to the CycD1 gene was confirmed by real-time PCR ChIP ( Figure 1 C) and indicates that LEF-1 cannot bind simultaneously to β-catenin and TLE1 in vivo, consistent with previous biochemical studies [10] ." + + + +
+ + + +
+ + + + + + 17113388 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Since TLE1 binds antagonistically with β-catenin to DNA-bound Lef-1, decreasing affinity for TLE1 would also favor transcriptional activation." + + + +
+ + + +
+ + + + + + 21075118 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ LEF1 binds TCF3 and CTNNB1. + + 2 / 2 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 2 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "LEF-1 normally binds with TCF-3 and β-catenin, forming transcriptional complexes that regulate the expression of cell fate genes [ xref ]." + + + +
+ + + +
+ + + + + + 29203441 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Β-catenin interactions with Lef1 and Tcf3 in the epidermis have been extensively characterised xref , xref ." + + + +
+ + + +
+ + + + + + 18213391 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds LEF1 and MITF. + + 2 / 2 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 2 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Β-catenin and LEF1 together bind to the MITF promoter via the binding site on LEF-1 and promote MITF expression [ xref , xref , xref , xref ]." + + + +
+ + + +
+ + + + + + 33332393 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "It has also been shown that β-catenin and Lef1 can directly interact with Mitf to induce Mitf-specific target genes in melanocytes xref , xref , indicating that Wnt/β-catenin signalling is important for maintenance of pigmented cells." + + + +
+ + + +
+ + + + + + 24324671 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ SMAD4 binds CTNNB1 and LEF1. + + 2 / 2 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 2 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Interestingly, Nishita et al. recently demonstrated that Smad4 forms a complex with β-catenin and Lef1, which regulates the expression of genes required for the formation of the organizer in Xenopus [102] ." + + + +
+ + + +
+ + + + + + 12651222 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The two pathways were found to converge at the promoter of Xtwn , where Smad4, β-catenin, and Lef1 form a complex and bind to adjacent regulatory elements to co-regulate Xtwn expression." + + + +
+ + + +
+ + + + + + 19002158 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ VDR binds LEF1 and CTNNB1. + + 2 / 2 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 2 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We conclude that Krt15 and S1003A depend on β-catenin binding to ligand activated VDR and Lef1 for Wnt induction." + + + +
+ + + +
+ + + + + + 18213391 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "A novel interaction between the VDR and LEF1 (lymphoid enhancer-binding factor-1) that is independent of β-catenin was identified." + + + +
+ + + +
+ + + + + + 21471213 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Phosphorylated LEF1 binds CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The overall structures of non phosphorylated Lef-1 (1-63) and phosphorylated Lef-1 (1-63) bound to beta-catenin are almost identical, except that residues 26-41 of Lef-1 are visible in the phosphorylated structure, where they form an extended loop and participate in both intra- and intermolecular contacts (XREF_FIG)." + + + +
+ + + +
+ + + + + + 21075118 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ LEF1 binds GST and CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Β-catenin synthesized in vitro bound strongly and specifically to GST-LEF1 ( xref C, upper panel), but GAC63 synthesized in vitro did not ( xref C, lower panel)." + + + +
+ + + +
+ + + + + + 17344318 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ LEF1 binds LGALS12 and CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "For example, β-catenin enhanced interactions between Lef1 (GAL4-Lef1) and GRIP-1 (VP-GRIP), and this was primarily due to coactivation and interactions of β-catenin with Lef1 but not GRIP-1." + + + +
+ + + +
+ + + + + + 21169420 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ TGFB3 binds LEF1 and CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The downstream effects of TGF-β3 signaling causes LEF-1 gene transcription which then associates with β-catenin and results in either suppression or repression of EMT genes as described above. xref Thus, a complex interplay of the three isoforms is involved in EMT." + + + +
+ + + +
+ + + + + + 22561306 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds LEF1 and NR4A2. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "36 These data show that Wnt signaling, specifically through β-catenin, enhances NR4A2 activity and, conversely, that NR4A2 influences β-catenin activity through direct physical interaction of NR4A2 with β-catenin and LEF1." + + + +
+ + + +
+ + + + + + 19549529 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds LEF1 and GAPDH. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Β-catenin did not bind to the GAPDH promoter that did not have the LEF-1 binding sites." + + + +
+ + + +
+ + + + + + 23396279 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ LEF1 binds CTNNB1 and Cohesin. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Treatment of hESCs with Wnt3a induces binding of β-catenin and cohesin to LEF-1 sites and directs enhancer looping to nearby ME target gene promoters, activating transcription in a cohesin-dependent manner." + + + +
+ + + +
+ + + + + + 25936800 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ PSTPIP1 binds CTNNB1 and LEF1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Endogenous HPIP or β-catenin associated with endogenous LEF1 in the nucleus (Supplementary Fig.  xref )." + + + +
+ + + +
+ + + + + + 30659184 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds LEF1 and EP300. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Collectively, the results indicate that combined glucose and LiCl treatment increases p300-LEF-1-β-catenin interaction while preventing SIRT1-LEF-1 and SIRT1-β-catenin interaction and suggest that increased acetylation by p300 may be required for nuclear retention of the LEF-1/β-catenin complex." + + + +
+ + + +
+ + + + + + 23273980 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ LEF1 binds HNF4A and CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The expression of perivenous genes was also associated with the interaction of β-catenin with LEF1 and hepatocyte nuclear factor 4-α (HNF4α) that could also be detected with higher levels in the perivenous area xref ." + + + +
+ + + +
+ + + + + + 28126520 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds SMAD2_3 and LEF1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The nuclear pSmad2/3 can directly associate with the lymphoid enhancer binding factor 1/T cell-specific factor (LEF1/TCF) to synergistically activate β-catenin target genes." + + + +
+ + + +
+ + + + + + 27479195 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CD274 binds CTNNB1 and LEF1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "A chromatin immunoprecipitation (ChIP) assay with an anti–β-catenin or an anti–LEF-1 antibody showed that treatment of U87/EGFR cells with Wnt3A, EGF, or expression of CA β-catenin increased the binding of β-catenin and LEF-1 to the promoter region of CD274 ( xref )." + + + +
+ + + +
+ + + + + + 32860047 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ TNFRSF10B binds LEF1 and CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "This hypothesis agrees with the competition in vitro between E-cadherin cytosolic tail and Lef1 for binding to β-catenin 35 leading to the suppression of Lef1-mediated transactivation in SW480 cells." + + + +
+ + + +
+ + + + + + 20813963 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ LEF1 binds CTNNB1 and AXIN. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In String database, PITX2 was predicted to interact with LEF1, CTNNB1 and AXIN, all of which are the key factors of Wnt/β-catenin signaling pathway (Fig.  xref c)." + + + +
+ + + +
+ + + + + + 31043858 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds LEF1 and CDH1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "40,42,47–49 + Moreover, it has been shown that the LEF-1-β-catenin complex binds in vitro to the E-cadherin promoter to regulate the transcription of this gene, suggesting that although adhesion function and intracellular signaling activity of β-catenin are independent, they could be interrelated via negative regulation by E-cadherin." + + + +
+ + + +
+ + + + + + 9811344 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ APC binds CTNNB1 and LEF1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Loss of APC is associated with the accumulation of β-Catenin in the nucleus, which activates the T-cell factor (TCF) and the lymphoid enhancer factor (LEF) transcription factor as targets of the canonical Wnt pathway xref , xref ." + + + +
+ + + +
+ + + + + + 29549256 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CXCL1 binds CTNNB1 and LEF1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The full-length Tcf7 could efficiently bind to Gro2 ( xref ), β-catenin ( xref ), and Lef1 ( xref ), whereas the myc-Tcf7_ΔGroBD, myc-Tcf7_ΔN, and myc-Tcf7_ΔHMG could not bind to Gro2, β-catenin, and Lef1, respectively ( xref )." + + + +
+ + + +
+ + + + + + 32702011 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds PRMT6 and LEF1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "This opens the possibility that β-catenin and PRMT6 could simultaneously interact with LEF1." + + + +
+ + + +
+ + + + + + 34001852 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Tcf7l1-a binds LEF1 and CTNNB1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The N-termini of XTcf-3 and LEF-1 interact with the Armadillo repeat region of β-catenin ( Behrens et al. 1996; Huber et al. 1996; Molenaar et al. 1996 )." + + + +
+ + + +
+ + + + + + 9118222 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds LEF1 and RAC1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "To compare the interaction between these Rac1-specific mutants of β-catenin and LEF-1, a PLA was used." + + + +
+ + + +
+ + + + + + 26403202 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ EPCAM binds CTNNB1 and LEF1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Concurrently, we designed peptides for targeting the intracellular domain of EpCAM ( xref ), which interacts with β-catenin and Lef1 to form a nuclear complex that regulates β-catenin-dependent transcription ( xref )." + + + +
+ + + +
+ + + + + + 21256838 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds AR and LEF1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "While beta-catenin can bind directly to both AR and Lef1, GRIP1 can only bind directly to AR; the ability of GRIP1 to associate with and function as a coactivator for Lef1 is entirely dependent on the presence of beta-catenin." + + + +
+ + + +
+ + + + + + 14638683 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds LEF1 and SMAD7. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 15684397 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ LEF1 binds CTNNB1 and JUP. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Transcriptional responses induced by Wnt depend on the association of either beta-catenin or gamma-catenin with lymphoid enhancer factor/T cell factor transcription factors." + + + +
+ + + +
+ + + + + + 17906078 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ LEF1 binds CTNNB1 and LHX3. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The EpCAM intracellular domain (EpICD) peptide translocates to the cell nucleus following proteolytic cleavage to assemble a transcriptional activation complex with LIM domains, β-catenin, Lef-1, and other transcription factors to activate Wnt target gene expression [ xref ]." + + + +
+ + + +
+ + + + + + 30467381 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ DLL1 binds CTNNB1 and LEF1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Research by Juan Galceran et al. [ xref ] confirmed that Lef1 binds to β-catenin in the nucleus to form the Lef1-β-catenin complex that activates the expression of endogenous Dll1 in fibroblasts." + + + +
+ + + +
+ + + + + + 23602012 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ HINT1 binds CTNNB1 and LEF1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In pull-down assays, HINT1 did not bind to β-catenin or LEF-1 nor did it impair the LEF-1/β-catenin interaction or the binding of pontin or reptin to β-catenin." + + + +
+ + + +
+ + + + + + 21316334 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 binds DKK2 and LEF1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "PitX2 also regulates the canonical Wnt signaling system through interactions with beta-catenin, dkk2 and Lef1, which in turn feedback onto PitX2 expression ( xref ; xref )." + + + +
+ + + +
+ + + + + + 21309065 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + + + + + + +
+
+
CTNNB1 activates LEF1.
+
+
+ + + + + + + + + + + + + + 2 + + + + + + 3 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 17 + + + + + + 87 + + + + + + +
+
+
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 activates LEF1. + + 101 / 101 + + +
+
+
+ + + + + + + + + + + + + + + + 3 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 17 + + + + + + 81 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Wnt3a signaling transiently stabilizes beta-catenin, allowing it to bind nuclear LEF-1 and TCF DNA binding proteins and activate target genes." + + + +
+ + + +
+ + + + + + 25936800 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "We show with antisense beta-catenin oligonucleotides that up-regulated LEF1 is not activated by beta-catenin in palate EMT." + + + +
+ + + +
+ + + + + + 14691138 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Thus far, the only major signaling pathway that has been consistently been shown to be directly involved in transformation of epithelium to mesenchyme is beta-catenin and lymphoid-enhancing factor 1, but whether or not beta-catenin will activate LEF1 depends on specific isoforms of LEF and TCF transcription factor that contain an alternative COOH-terminal " E " tail." + + + +
+ + + +
+ + + + + + 14691138 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Considering the wide-spread and successful use of beta-catenin to activate the LEF1 transcription factor, one might ask why use Smads instead?" + + + +
+ + + +
+ + + + + + 14691138 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Also, for the first time we present evidence that TGFbeta 3 up-regulates LEF1 mRNA and that Smads, not beta-catenin, activate LEF1 in this embryonic EMT." + + + +
+ + + +
+ + + + + + 14691138 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We show with antisense β-catenin oligonucleotides that up-regulated LEF1 is not activated by β-catenin in palate EMT." + + + +
+ + + +
+ + + + + + 14691138 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Thus far, the only major signaling pathway that has been consistently been shown to be directly involved in transformation of epithelium to mesenchyme is β-catenin/lymphoid-enhancing factor 1 (LEF1; xref ; xref ), but whether or not β-catenin will activate LEF1 depends on specific isoforms of LEF/TCF transcription factor that contain an alternative COOH-terminal “E” tail ( xref )." + + + +
+ + + +
+ + + + + + 14691138 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Next, we looked at the possibility that normal palates are not using β-catenin–activated LEF1 to transform the MEE to mesenchyme." + + + +
+ + + +
+ + + + + + 14691138 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "These findings indicate that beta-catenin alone can mediate the nuclear import of lef-1 through the direct binding." + + + +
+ + + +
+ + + + + + 15936755 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "By bioinformatics analyses, we discovered that the promoter regions of all RAS genes contained putative T-cell factor (TCF)/lymphoid enhancer factor (LEF)-binding sites, and beta-catenin induced the binding of LEF-1 to these sites in kidney tubular cells." + + + +
+ + + +
+ + + + + + 25012166 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "These results demonstrate that forced expression of Dvl-1 elevates NANOG expression, probably due to the accumulation of β-catenin, which can activate the Lef1." + + + +
+ + + +
+ + + + + + 21689639 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Tcf7l1 forms a complex with beta-catenin and thereby loses chromatin occupancy in mouse embryonic stem cells and breast cancer cells XREF_BIBR, whereas recombinant beta-catenin strongly promotes binding of Lef1 to chromatin templates in vitro XREF_BIBR." + + + +
+ + + +
+ + + + + + 28198400 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The c-myc gene has been identified as a direct target of LEF-1 and TCF proteins, which are repressed by wild-type APC and activated by beta-catenin in colon cancer cells [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 26219398 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Moreover, we demonstrate that activation of beta-catenin and Lef -1 signaling by Wnt-1 or by overexpression of beta-catenin itself is inhibited by caveolin-1 expression." + + + +
+ + + +
+ + + + + + 10816572 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Thus, Wnt signaling increases cytoplasmic levels of beta-catenin, which enters the nucleus and interacts with other factors to activate a TCF and LEF1 mediated transcriptional program 5." + + + +
+ + + +
+ + + + + + 20890287 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "WNT signalling culminates in the accumulation of β-catenin, which activates the T cell factor (TCF)–lymphoid enhancer factor (LEF) transcription factor complex that induces the expression of target genes such as MYC ." + + + +
+ + + +
+ + + + + + 23594855 + + + + +
+
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+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "Both VDR and 1,25 (OH) 2 D suppress beta-catenin stimulated LEF1 and TCF driven reporter activity." + + + +
+ + + +
+ + + + + + 25445917 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Thus, beta-catenin accumulates, enters the nucleus and activates genes acting as a co-activator of the transcription factors belonging to the T cell factor and lymphoid enhancer factor-1 (TCF and LEF1) family [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 29462960 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "We have shown previously that promoter 1 of the LEF1 gene is activated by T cell factor (TCF)-beta-catenin complexes in transient transfection assays, suggesting that LEF1 is a target of the Wnt pathway in colon cancer." + + + +
+ + + +
+ + + + + + 12582159 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Relationships between hypoxia and Wnt signaling have been explored in neural stem cells where HIF-1alpha enhances beta-catenin activation and expression of downstream effectors LEF-1 and TCF-1 XREF_BIBR." + + + +
+ + + +
+ + + + + + 26861754 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "The binding of canonical Wnt proteins to members of the Frizzled receptors (Fzd) and its co-receptors results in the activation of Dishevelled and inhibition of the beta-catenin degradation complex, allowing targeting of T-cell specific transcription factor and lymphoid enhancer binding factor 1 (TCF/LEF) family of transcription factors and transcriptional activation of Wnt target genes XREF_BIBR, XREF_BIBR." + + + +
+ + + +
+ + + + + + 29872092 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "It has been shown that in chick neural cells, phosphorylation of beta-catenin at tyrosine 489 (Y489) targets it to the nucleus where it binds to its partner (s) TCF and Lef1 and acts as a co-activator of transcription XREF_BIBR." + + + +
+ + + +
+ + + + + + 25003522 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Importantly, the beta-catenin targets LEF-1 and CD44 remained expressed at elevated levels and ectopically throughout the crypt-villus axis in triple mutant mice, indicating that ablation of YAP and TAZ does not modify ectopic beta-catenin activity induced by the APC mutation." + + + +
+ + + +
+ + + + + + 24976009 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "This result is somewhat consistent with the findings that Wnt and beta-catenin pathways induce the 2.5 kb Lef-1 promoter in cell lines (Filali et al, 2002) and that Shh-knockout mice lack Wnt5a mRNA induction during hair-follicle morphogenesis (Reddy et al, 2001)." + + + +
+ + + +
+ + + + + + 15245424 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "The up-regulation of Wnt1 expression and activation of the WNT1 and beta-catenin signaling pathway in the adult VM, however, might contribute at least in part to the increased proliferation of locally existing progenitor cells (OPCs and others) in these genetic and neurotoxin based rodent models of PD.The ectopic expression of Wnt1 in the adult En1 +/Wnt1 VM activated a gene cascade consisting of the direct WNT and beta-catenin targets Lef1, Lmx1a, Fgf20, Dkk3 and potentially also En1, and the indirect targets Pitx3 (activated by LMX1A) and Bdnf (activated by PITX3)." + + + +
+ + + +
+ + + + + + 26049140 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "However, Wnt5a and Wnt4, which neither elevate the level of cytosolic beta-catenin nor activate LEF1 dependent transcriptional activity (Shimizu et al., 1997), did not increase ALP activity in C3H10T1/2 and ST2 cells." + + + +
+ + + +
+ + + + + + 11719191 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "As noted previously [11], beta-catenin strongly enhances binding of LEF-1 to chromatin templates, and CK2 enhanced this effect." + + + +
+ + + +
+ + + + + + 17113388 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "However, the authors reported that tyrosine phosphorylation of beta-catenin does not change its binding affinity to LEF-1 nor enhances cyclin D1 transactivation, a nuclear target of beta-catenin and LEF -1 [21]." + + + +
+ + + +
+ + + + + + 20840866 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "RAS genes contain putative T cell factor (TCF)/lymphoid enhancer factor (LEF)-binding sites in their promoter regions, and beta-catenin induces the binding of LEF-1 to these sites in kidney tubular cells." + + + +
+ + + +
+ + + + + + 31392659 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Then activated β-catenin in turn activates downstream transcriptional factors, T-cell factor (TCF) and lymphoid enhancer factor (LEF) to further regulate the targeted genes [ xref , xref ]." + + + +
+ + + +
+ + + + + + 32669974 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "In fact, beta-catenin activates TCF and Lef1 supporting mesenchymal transition (28)." + + + +
+ + + +
+ + + + + + 25207459 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Of note, β-catenin binds to Lef1 and activates Lef1 transcription complex, leading to down-regulation of E -cadherin expression [ xref ]." + + + +
+ + + +
+ + + + + + 33388549 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
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+ + + +
+ + + + + "In the nucleus, β-catenin binds and activates the lymphoid enhancer factor (LEF)/T cell factor (TCF) transcription factor to regulate the expression of Wnt target genes ( xref )." + + + +
+ + + +
+ + + + + + 33071819 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "beta-Catenin does not bind to the DNA but directs TCF and LEF1 to regulate the genes responsible for cell proliferation." + + + +
+ + + +
+ + + + + + 27919787 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "As a result, the beta-catenin is accumulated in the cytoplasm and translocated to the nucleus where it interacts with and activates TCF and Lef1 transcription complex initiating Wnt activated gene expression [XREF_BIBR, XREF_BIBR, XREF_BIBR]." + + + +
+ + + +
+ + + + + + 33814008 + + + + +
+
+
+ + + +
+
+
+
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+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "Down-regulation of β-catenin by β-catenin shRNA reduced LEF-1 promoter activity (Fig. 10e), whereas overexpression of β-catenin enhanced LEF-1 promoter activity (Fig. 10f)." + + + +
+ + + +
+ + + + + + 31174562 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
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+ + + +
+ + + + + "β‐catenin can activate lymphoid enhancing factor‐1 (LEF‐1) at the transcription level." + + + +
+ + + +
+ + + + + + 30556279 + + + + +
+
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+ + + +
+
+
+
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+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "The online PROMO algorithm determines a putative LEF-1 binding site on LINC01278 promoter, the LEF-1 binds to the putative promoter site of LINC01278 gene, and beta-catenin enhances the binding of LEF-1 to the LINC01278 gene promoter." + + + +
+ + + +
+ + + + + + 34273985 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "The results of ChIP showed that overexpression of β-catenin increased the binding of LEF-1 to the LINC01278 promoter (Fig. 3A)." + + + +
+ + + +
+ + + + + + 34273985 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "ChIP experiments also confirmed the endogenous binding of the transcription factor LEF-1 to the LINC01278 promoter, and showed that β-catenin can enhance the binding of LEF-1 to the LINC01278 promoter." + + + +
+ + + +
+ + + + + + 34273985 + + + + +
+
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+ + + +
+
+
+
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+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "Degradation of phosphorylated β-catenin limits β-catenin nuclear translocation to inactivate LEF1 translation, resulting in an inhibited Wnt/β-catenin signaling activation." + + + +
+ + + +
+ + + + + + 34326690 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "There are putative TCF/LEF binding sites in the RAS promoter region through bioinformatics analyses, and β-catenin could trigger LEF-1 to bind to these sites in renal tubular cells (Zhou et al., 2015b)." + + + +
+ + + +
+ + + + + + 34483931 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "CEMP1-p4 stimulation upregulated the expression of beta-catenin and glycogen synthase kinase 3 beta (GSK-3B) and activated the transcription factors TCF1/7 and Lymphoid Enhancer binding Factor 1 (LEF1) at the mRNA and protein levels." + + + +
+ + + +
+ + + + + + 32075221 + + + + +
+
+
+ + + +
+
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+
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+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "In this study, DACT2 decreased the expression of active β-catenin and its downstream genes in NPC cells and suppressed the activity of the β-catenin/LEF1 complex." + + + +
+ + + +
+ + + + + + 30359298 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
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+ + + +
+ + + + + "The other negative regulator SOX17 repress the β-catenin dependent spatial and temporal LEF-1 activation [ xref ]." + + + +
+ + + +
+ + + + + + 32726949 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "Cotransfection of beta-catenin and LEF-1 into Chinese hamster ovary cells induced transactivation of a LEF-1 reporter, which was blocked by the N-cadherin-derived molecules." + + + +
+ + + +
+ + + + + + 9860970 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "Because scales develop in an invariant sequence we were also able to analyze expression of conserved Wnt and beta-catenin targets lef1 and axin2 in fixed specimens." + + + +
+ + + +
+ + + + + + 30014845 + + + + +
+
+
+ + + +
+
+
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+
+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "These experiments demonstrated that 1 h of laminar FSS (10 dynes/cm 2)-induced translocation of beta-catenin from the cytoplasm to the nucleus and activated an LEF-1 and TCF reporter gene." + + + +
+ + + +
+ + + + + + 21479153 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "In these clusters we observed the expression of cell survival and cell cycle genes CCND2, NFKB1, PLK1, NAIP; putative oncogenes JUNB, TOX, AHI1; novel cancer testis genes GTSF1, SYCP1 as well as embryonic stem cell genes TCF3, EVA1, CHD1; genes promoting inflammatory T cell signaling ITK, LCK, FYB, GNLY, CCL18, CCL26, E-Selectin; skin homing chemokine receptor CCR4; cytokines (and their cognate receptors) that were reported to be secreted by the Th17 cells IL-26, IL-17A, IL-17F, IL-21 and IL-21R; the IL-22 cytokine; actin binding protein PLS3; matrix metalloproteinase MMP12; downstream positive regulator of WNT and beta-catenin signalling LEF1; transcription factors STAT5A, MXI and POU2AF; markers of T cell activation TFRC, IRF4; and other signaling genes including T3JAM, FOSL1, SHD1A, SERPINB4 (XREF_FIG, XREF_FIG and XREF_SUPPLEMENTARY)." + + + +
+ + + +
+ + + + + + 25779945 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "These authors additionally demonstrated that Wt1 knockout resulted in an epicardium specific reduction in beta-catenin, with down-regulation of the Wnt / beta-catenin target Lef1 [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 26907357 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "Furthermore, GRIP1 and beta-catenin can synergistically enhance the activity of both AR and Lef1, and both coactivators are recruited specifically to AR driven and Lef1 driven promoters." + + + +
+ + + +
+ + + + + + 14638683 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
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+ + + +
+ + + + + "This naturally occurring Lef-1 transcript was used in order to eliminate the effect of β-catenin activating Lef-1." + + + +
+ + + +
+ + + + + + 17068080 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "It also showed that betacatenin relieves Tcf3 repression of Lef1, and subsequently activate Wnt target genes through its interaction with Lef1." + + + +
+ + + +
+ + + + + + 29383478 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
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+ + + +
+ + + + + "Here, we show that Hypoxia Inducible Factor-1α (HIF-1α), a principal mediator of hypoxic adaptations, modulates Wnt/β-catenin signalling in hypoxic embryonic stem (ES) cells by enhancing β-catenin activation and expression of downstream effectors LEF-1 and TCF-1." + + + +
+ + + +
+ + + + + + 20852629 + + + + +
+
+
+ + + +
+
+
+
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+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "To specifically target cells that activate the Wnt and beta-catenin pathway in the lesion site, we generated a TetActivator line using regulatory elements of the direct Wnt and beta-catenin target lef1 (lef1 : TetA AmCyan; Supplementary Fig. 4b)." + + + +
+ + + +
+ + + + + + 28743881 + + + + +
+
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+ + + +
+
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+
+
+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "Recently, for endometrial cancer similar observations have been described confirming promoter binding sites for the Wnt and beta-catenin inducing transcription factor LEF-1 and, interestingly, also for the EMT inducing transcription factors SNAI1 and SNAI2 XREF_BIBR." + + + +
+ + + +
+ + + + + + 22295114 + + + + +
+
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+ + + +
+
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+
+
+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "Mazumdar et al., have demonstrated that Hif1a modulates Wnt and beta-catenin signaling in hypoxic embryonic stem (ES) cells by enhancing beta-catenin activation and expression of the downstream effectors Lef-1 and Tcf-1." + + + +
+ + + +
+ + + + + + 25565969 + + + + +
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+ + + +
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+ +
+
+ + + +
+ + + + + "This naturally occurring Lef-1 transcript was used in order to eliminate the effect of beta-catenin activating Lef-1." + + + +
+ + + +
+ + + + + + 17068080 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In fact, a balance of stimulation and suppression of genes by HNF4alpha is influenced by the beta-catenin activated transcription factor LEF1 to establish zonal specific expression of various enzymes (e.g. glutamine synthetase)." + + + +
+ + + +
+ + + + + + 29112863 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "In fact, a balance of stimulation and suppression of genes by HNF4α is influenced by the β-catenin activated transcription factor LEF1 to establish zonal specific expression of various enzymes (e.g. glutamine synthetase)." + + + +
+ + + +
+ + + + + + 29112863 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "beta-Catenin stabilizes cell-cell junctions by anchoring cell adhesion molecules (i.e., Cadherins) in the actin cytoskeleton, activates the LEF1 and TCF family of transcription factors, and is involved in the amplification and separation of centrosomes [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 23377854 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Since LEF1 is strongly induced by Wnt and beta-catenin in Ewing sarcoma cells we speculate that this might lead to sequestration of EWS and ETS proteins by LEF1 and inhibition of EWS and ETS dependent transcription." + + + +
+ + + +
+ + + + + + 27364557 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The LEF1 gene is aberrantly transcribed in colon cancers because promoter 1 (P1) is a Wnt target gene and is activated by TCF–β-catenin complexes." + + + +
+ + + +
+ + + + + + 20525792 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "We hypothesize that endothelial cells are responsive to Wnt signals and that Lef1, a member of the vertebrate specific Wnt and beta-catenin throughput inducing transcription factors ' sub-family Lef1 and Tcf1, mediates this responsiveness and promotes endothelial cell invasion." + + + +
+ + + +
+ + + + + + 22168911 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Beta-catenin relieves I-mfa-mediated suppression of LEF-1 in mammalian cells." + + + +
+ + + +
+ + + + + + 17090604 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In proximal tubular cells, constitutively activated beta-catenin promotes the binding of LEF-1 to these sites, and overexpression of beta-catenin or various Wnt ligands induces expression of multiple RAS genes (XREF_FIG) [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 26808707 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Ectopic overexpression of beta-catenin in 293 cells also induced the assembly of the beta, catenin, and LEF-1 complex and activated gene transcription from a LEF-1-dependent promotor." + + + +
+ + + +
+ + + + + + 9419974 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The elimination of Wnt and beta-catenin signaling in either Lef1 or Wnt10b knockout mice resulted in down-regulation of Shh expression." + + + +
+ + + +
+ + + + + + 17284610 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "For instance, PIASy directs the Wnt and beta-catenin mediator LEF1 to PML nuclear bodies, which results in repression of LEF1 activity." + + + +
+ + + +
+ + + + + + 20421208 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Most importantly, the nuclear accumulation of beta-catenin activated T-cell factor and lymphocyte enhancer factor-1 (TCF-1 and LEF-1), which acts as a transcriptional activator." + + + +
+ + + +
+ + + + + + 26872378 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "It has been reported to target the mRNA of Lef1, the transcription factor that is upregulated by beta-catenin [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 25796440 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Genetic mutations or altered protein expression of beta-catenin and Apc have been implicated in human cancers, and all result in increased beta-catenin levels, which in turn lead to increased Lef-1 and Tcf-1 transcriptional activity and deregulated proliferation [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 12559040 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "PITX2 isoforms regulate the LEF-1 promoter, and beta-catenin synergistically enhanced activation of the LEF-1 promoter in combination with PITX2 and Lef-1 isoforms." + + + +
+ + + +
+ + + + + + 17785445 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "69 Finally, HIF1alpha itself modulates Wnt and beta-catenin signaling in hypoxic embryonic stem (ES) cells by enhancing beta-catenin activation and expression of the downstream effectors LEF-1 and TCF-1." + + + +
+ + + +
+ + + + + + 21763962 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Furthermore, co-expression of beta-catenin and DBC1 synergistically enhanced LEF1 activity." + + + +
+ + + +
+ + + + + + 30082743 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "We observed that G-17 not only enhanced the expression of total cellular beta-catenin, but also increased nuclear beta-catenin accumulation and beta-catenin-dependent LEF-1 activity." + + + +
+ + + +
+ + + + + + 15798764 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "TGF-β signaling can directly increase LEF1 expression through SMADs and inhibit glycogen synthase kinase 3β (GSK-3β) through the phosphoinositide 3-kinase (PI3K)–Akt pathway, which enables β-catenin–dependent activation of LEF-1 to induce EMT ( xref , xref )." + + + +
+ + + +
+ + + + + + 25249658 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "CTNNB1 activates Lef1 transcription and upregulates Lef1 promoter activity in vitro." + + + +
+ + + +
+ + + + + + 25033758 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In situ hybridization experiments for the Wnt and beta-catenin targets lef1 and ctnnb2 revealed that lef1 and ctnnb2 are expressed in deposited interneuromast cells at 2 dpf (XREF_FIG, arrowheads)." + + + +
+ + + +
+ + + + + + 24642408 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "We performed in situ hybridization with the Wnt and beta-catenin target lef1 and a dgfp probe for a transgenic Wnt and beta-catenin reporter line, Tg (Tcf and Lef-miniP : dGFP) that contains 6 copies of a consensus TCF/Lef binding site followed by destabilized EGFP." + + + +
+ + + +
+ + + + + + 24642408 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "After Wnt binds to cell-surface receptors Fzd and Lrp, beta-catenin is stabilized in the cytoplasm and translocated to the nucleus where it activates the Tcf and Lef1 transcription complex to regulate the promoter activity of Wnt signaling target genes [XREF_BIBR, XREF_BIBR]." + + + +
+ + + +
+ + + + + + 24115331 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Here, we show that Hypoxia Inducible Factor-1alpha (HIF-1alpha), a principal mediator of hypoxic adaptations, modulates Wnt and beta-catenin signalling in hypoxic embryonic stem (ES) cells by enhancing beta-catenin activation and expression of downstream effectors LEF-1 and TCF-1." + + + +
+ + + +
+ + + + + + 20852629 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "TCF-7 and LEF-1 transcription factors, which are represented by V$ LEF1TCF1_Q4, can be activated by beta-catenin and are involved in canonical WNT signaling." + + + +
+ + + +
+ + + + + + 27047536 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "TCF-7 and LEF-1 transcription factors, which are represented by V$LEF1TCF1_Q4, can be activated by β-catenin and are involved in canonical WNT-signaling (Brade et al., xref ; Chen et al., xref ; Pal and Khanna, xref ; Kwon et al., xref ; Naito et al., xref )." + + + +
+ + + +
+ + + + + + 27047536 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In the stem cell niche, Wnt signaling and beta-catenin stabilization are considered to activate the Lef1 and T-cell factor complex, which binds to its target genes and promotes stem cell activation and proliferation; these constitute critical steps required to support hair growth." + + + +
+ + + +
+ + + + + + 28810552 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Therefore, binding of beta-catenin to different interaction partners in the nucleus may direct both TCF and LEF1 dependent and -independent transcriptional regulation." + + + +
+ + + +
+ + + + + + 18506144 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "74 Ectopic expression of activated Akt did not appear to activate beta-catenin signaling in the cells examined as measured by changes in the levels of accumulation of cytosolic beta-catenin activation of LEF1 dependent transcription." + + + +
+ + + +
+ + + + + + 23778311 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In reporter gene assays using the pGL3OT reporter containing LEF responsive elements, beta-catenin enhanced LEF1 activity, and coexpression of beta-catenin and DBC1 further enhanced LEF1 function in a synergistic manner (XREF_FIG)." + + + +
+ + + +
+ + + + + + 26477307 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Consistent with the model in which beta-catenin acetylation enhances its binding to LEF1 and leads to increased chromatin occupancy of LEF1 by stabilizing LEF1, beta, and catenin complex, XREF_BIBR, XREF_BIBR our results further showed that DBC1 enhances the interaction of beta-catenin with LEF1 (XREF_FIG) and is required for efficient recruitment of LEF1 and beta-catenin to their target chromatin regions (XREF_FIG), probably through protecting beta-catenin from SIRT1 mediated deacetylation (XREF_FIG)." + + + +
+ + + +
+ + + + + + 26477307 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "PITX2, beta-catenin and LEF-1 interact to synergistically regulate the LEF-1 promoter." + + + +
+ + + +
+ + + + + + 15728254 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Lymphoid enhance factor1 (Lef1) is a transcriptional regulator of the Wnt and beta-catenin signaling cascade and is activated by nuclear beta-catenin." + + + +
+ + + +
+ + + + + + 20142103 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In the uninfected parental cell lines, stable expression full length LEF1 (variant 1) led to beta-catenin activation of an LEF1 responsive luciferase reporter." + + + +
+ + + +
+ + + + + + 29535816 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Reporter assays revealed that ectopic expression of Sox17 suppresses Wnt3A and beta-catenin activation of the Lef-1 promoter in cell lines." + + + +
+ + + +
+ + + + + + 20802155 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "This result strongly suggests that the most conserved (by position and sequence similarity among five mammalian species) and proximal (relative to the TSS) Lef1 and Tcf binding site ' c ' is the functionally most important of the three Lef1 and Tcf binding sites for Lef1 mediated activation of the murine Dkk3 gene by Wnt1 and beta-catenin signaling." + + + +
+ + + +
+ + + + + + 25145340 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Moreover, CK1 dependent phosphorylation in contrast to CK2 disrupts the association of beta-catenin and LEF-1 but does not impair DNA binding of LEF-1." + + + +
+ + + +
+ + + + + + 15747065 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Thus, miR-26b is a tumor repressor that is a potent inhibitor of colon cancer cell proliferation that blocks Wnt and beta-catenin dependent activation of LEF-1 and a model for tumor suppressor like activity of miR-26b is illustrated in XREF_FIG." + + + +
+ + + +
+ + + + + + 24785257 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Ten genes (CCND1, JUN, CCND2, EGFR, LEF1, MET, MMP7, MYC, TCF3, TERT, and beta-catenin itself (CTNNB1)) were up-regulated by beta-catenin and two (FOS and CDH1) were down-regulated; for the remaining genes, the directionality of the beta-catenin effect was not reported." + + + +
+ + + +
+ + + + + + 26509276 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Expression analysis of a selection of these transcripts demonstrates a similar profile, suggesting interaction and or co-regulation of Wnt and beta-catenin antagonists, Wnt and beta-catenin target element TCF4, and EMT related transcription factors SNAI2 and LEF1, which can be activated by both Wnt and beta-catenin and TGF-beta signalling (XREF_FIG) XREF_BIBR." + + + +
+ + + +
+ + + + + + 26783251 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "Activated dvl binds and inhibits the phosphorylation of beta catenin by gsk3beta/alfa, blocking beta catenin degradation), so that beta catenin accumulates and translocates to the nucleus, where it interacts with the t cell specific factor (tcf)/lymphoid enhancer binding factor 1 (lef-1) transcription factor and induces the transcription of target genes such as c-jun, c-myc, and cyclin d1" + + + +
+ + + +
+ + + + + + 15735151 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "Upon wnt activation, cytoplasmic beta-catenin is stabilized and enters the nucleus, where it associates with transcription factors, notably tcf (t cell factor) and lef (lymphoid enhancer-binding factor), to regulate the transcription of target genes. Thus beta-catenin regulates gene expression by direct interaction with transcription factors such as lef-1, providing a molecular mechanism for the transmission of signals, from cell-adhesion components or wnt protein to the nucleus." + + + +
+ + + +
+ + + + + + 23151663 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "Phosphorylated lrp5/6 leads to inhibition of the so-called beta-catenin destruction complex (which includes axin, gsk3, dvl, ck1, and the tumor suppressor adenomatous polyposis coli), resulting in the stabilization and translocation of beta-catenin in the nucleus, where it activates target genes through binding to tcf/lef transcription factors." + + + +
+ + + +
+ + + + + + 21078818 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Transcriptionally active CTNNB1 activates LEF1. + + 2 / 2 + + +
+
+
+ + + + + + + + + + + + + + 2 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "In response to Wnt, beta-catenin is stabilized and translocated into the nucleus where it stimulates gene expression through Tcf/Lef." + + + +
+ + + +
+ + + + + + 10921920 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + "from full text - Figure 1 " + + + +
+ + + +
+ + + + + + 16484682 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to LEF1 activates LEF1. + + 2 / 2 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 2 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Similarly, the interaction between nuclear beta-catenin and TCF-4 or LEF-1 was reduced by CaSR activation, indicating an inhibitory association of beta-catenin and TCF-4 or LEF-1 in the nucleus." + + + +
+ + + +
+ + + + + + 27108064 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Of note, beta-catenin binds to Lef1 and activates Lef1 transcription complex, leading to down-regulation of E-cadherin expression [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 33388549 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1-S37A activates LEF1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Furthermore, we observed that MG132 also rescued the inhibitory effect of DDIP on the Lef-1 luciferase activity induced by beta-catenin S37A, a constitutively active beta-catenin lost the binding site for the E3 ligase and un degraded [1,26]." + + + +
+ + + +
+ + + + + + 20603214 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to PITX2 activates LEF1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "For example, Pitx2, a paired-homeodomain containing transcription factor (Prd), can directly bind to beta-catenin and synergistically activate the promoter of Lef-1 XREF_BIBR." + + + +
+ + + +
+ + + + + + 23383281 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to TCF4 activates LEF1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Similarly, the interaction between nuclear beta-catenin and TCF-4 or LEF-1 was reduced by CaSR activation, indicating an inhibitory association of beta-catenin and TCF-4 or LEF-1 in the nucleus." + + + +
+ + + +
+ + + + + + 27108064 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to its activates LEF1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The phosphorylated alpha-catenin loses its binding to beta-catenin, which subsequently activates beta-catenin-TCF and LEF -1 transcriptional activity." + + + +
+ + + +
+ + + + + + 19941816 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + + + + + + +
+
+
CTNNB1 increases the amount of LEF1.
+
+
+ + + + + + + + + + + + 5 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 19 + + + + + + +
+
+
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 increases the amount of LEF1. + + 19 / 19 + + +
+
+
+ + + + + + + + + + + + 5 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 14 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Beta-catenin has been shown to activate LEF-1 transcription during EMT induced in vitro by c-Fos." + + + +
+ + + +
+ + + + + + 12095232 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Inducible epithelial Wnt10a or beta-catenin deletion caused absence of nuclear, or all, beta-catenin, respectively (XREF_FIG), and loss of LEF1 and HOXC13 expression (XREF_FIG)." + + + +
+ + + +
+ + + + + + 28589954 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "These data suggest that Lef1 mRNA expression is directly regulated by Wnt and beta-catenin signaling in the developing tooth mesenchyme." + + + +
+ + + +
+ + + + + + 19631205 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Thus, FLAP1 enhanced LEF1 and TCF mediated transcription (XREF_FIG) and beta-catenin dependent transcription (XREF_FIG), while full-length Fli-I acted as a negative regulator of beta-catenin-dependent transcription (XREF_FIG)." + + + +
+ + + +
+ + + + + + 16990252 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "15,16 Although transcription of both TCF-1 and LEF-1 is up-regulated by beta-catenin nuclear signaling, 15,16 it is not yet clear how the differential expression of their isoforms is controlled." + + + +
+ + + +
+ + + + + + 11839557 + + + + +
+
+
+ + + +
+
+
+ + + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 12582159 + + + + +
+
+
+ + + +
+
+
+ + + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 12052822 + + + + +
+
+
+ + + +
+
+
+ + + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 17893322 + + + + +
+
+
+ + + +
+
+
+ + + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 12582159 + + + + +
+
+
+ + + +
+
+
+ + + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 15728254 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The Wnt and beta-catenin activation in CMs by Apc deletion increased Lef1 and Tcf7 levels, but suppressed Tcf7l2 expression." + + + +
+ + + +
+ + + + + + 30778164 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Knockdown of Becn1 led to an increased expression of Lef1 from reprogramming day 5, suppressed expression of Wnt inhibitors including Sfrp1/2, and translocation of β-catenin into nucleus that subsequently transactivated downstream gene expression." + + + +
+ + + +
+ + + + + + 33087505 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Thus, in the absence of beta catenin mediated canonical Wnt signaling, Bmp4 was insufficient to maintain Lef1 expression in the developing tooth mesenchyme and suggested that Lef1 mRNA expression is directly regulated by Wnt and beta catenin signaling in the developing tooth mesenchyme." + + + +
+ + + +
+ + + + + + 26604501 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "CTNNB1 activates Lef1 transcription and upregulates Lef1 promoter activity in vitro." + + + +
+ + + +
+ + + + + + 25033758 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Moreover, Lef1 mediated transcription under basal conditions or stimulated by stabilization of beta-catenin by inactivating GSK3beta with LiCl is similar in scramble- and Cx43 silenced MLO-Y4 cells." + + + +
+ + + +
+ + + + + + 23483620 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "These data suggest that Wnt and beta-catenin signaling induces Lef1 expression, thereby decreasing Sema3A expression in odontogenic epithelial cells." + + + +
+ + + +
+ + + + + + 30862786 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "beta-CATENIN has been shown to activate LEF-1 transcription in regulating the expression of several EMT related genes during the EMT [XREF_BIBR], and FOXM1 has been shown to maintain the nuclear SMAD3 and SMAD4 complex [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 25537512 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The systematic nuclear localization of beta-catenin in H5 derivatives that are dedifferentiated or that show imperfect restoration of the hepatic phenotype led us to investigate the expression of LEF-1, the nuclear partner of beta-catenin." + + + +
+ + + +
+ + + + + + 9472044 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Activation of Wnt and beta-Catenin signaling increases the expression of ZNRF3 3, LEF1, Cyclin D1 36 and AXIN2, which are direct targets of beta-Catenin XREF_BIBR, XREF_BIBR, XREF_BIBR." + + + +
+ + + +
+ + + + + + 29872083 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Modified CTNNB1 increases the amount of LEF1. + + 2 / 2 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 2 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "However, the co-expression of FLAP1, p300 and beta-catenin caused synergistic enhancement of LEF1 and TCF mediated transcription (bar 8)." + + + +
+ + + +
+ + + + + + 16990252 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "This increase in beta-catenin expression would be expected to interact with and increase TCF and LEF1 target gene expression in these cells, a pathway contributing to breast cancer progression." + + + +
+ + + +
+ + + + + + 24534923 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 increases the amount of sumoylated LEF1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "LEF-1 and TCF-4 sumoylation (by the SUMO ligase PIASy) represses LEF-1 activity by targeting it to nuclear bodies but enhances TCF-4 and beta-catenin transcription, while CBP mediated acetylation of TCF results in decreased TCF and beta-catenin-binding in Drosophila and increased TCF nuclear retention in nematodes, both leading to transcriptional repression." + + + +
+ + + +
+ + + + + + 19619488 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to LEF1 increases the amount of LEF1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In colon cancer cells, beta-catenin and LEF1 complexes drive transcription of the full-length LEF1 isoform that can bind beta-catenin at the expense of a dominant negative isoform." + + + +
+ + + +
+ + + + + + 26509276 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to PITX2 increases the amount of LEF1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Beta-catenin directly interacts with PITX2 to synergistically regulate LEF-1 expression." + + + +
+ + + +
+ + + + + + 15728254 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + + + + + + +
+
+
CTNNB1 inhibits LEF1.
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + 1 + + + + + + + + + + + + 2 + + + + + + 11 + + + + + + +
+
+
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 inhibits LEF1. + + 12 / 12 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + 1 + + + + + + + + + + + + 2 + + + + + + 9 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "A constitutively active beta-catenin enhanced LEF1 dependent repression of Runx2." + + + +
+ + + +
+ + + + + + 12551949 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "A constitutively active beta-catenin enhanced Lef1 dependent repression of Runx2 [30]." + + + +
+ + + +
+ + + + + + 23911749 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "(53) Crucially, it has been shown that constitutive beta-catenin mediated activation of LEF-1 represses the osteoblast transcriptional regulator, Runx2, and subsequent maturation of osteoblasts." + + + +
+ + + +
+ + + + + + 33778326 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Moreover, siRNA mediated depletion of beta-catenin reduced the association of FOXG1 and LEF-1, indicating that the association of FOXG1 with LEF-1 is mediated by beta-catenin." + + + +
+ + + +
+ + + + + + 31771611 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The results showed that Nek2B increased LEF-1 promoter activity, which was reversed by suppression of β-catenin (Fig. 10g)." + + + +
+ + + +
+ + + + + + 31174562 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "CTNNB1 is negatively regulated by APC, transducing wingless signals and interacting with components of the LEF1 and TCF4 transcription complexes, urokinase, and PSEN1." + + + +
+ + + +
+ + + + + + 36330413 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "N-cadherin cytoplasmic domain sequesters β-catenin and reduces its ability to induce lymphocyte enhancer-binding factor 1 (LEF-1)-responsive transactivation in Chinese hamster ovary cells. xref In cultured porcine and juvenile human NP cells, N-cadherin appears to promote cell clustering and NP-like morphology, correlating with β-catenin nuclear translocation. xref It would be interesting to examine if β-catenin inhibits the constitutive LEF-1 responsive transactivation xref in the NP cells." + + + +
+ + + +
+ + + + + + 32858534 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ trips + +
+ +
+
+ + + +
+ + + + + "Beta-catenin relieves I-mfa-mediated suppression of LEF-1 in mammalian cells." + + + +
+ + + +
+ + + + + + 17090604 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The disruption through gene mutation of these key beta-catenin degradation components is known to increase the protein levels of beta-catenin which then translocates to the nucleus and activates LEF-1 and TCF transcription factors and gene networks that promote CRC development." + + + +
+ + + +
+ + + + + + 26930278 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "In fact, in human CD34 + hematopoietic progenitor cells, inhibition of LEF1 but not of beta-catenin, impaired proliferation and apoptosis mechanisms of this cell population, supporting the hypothesis of a beta-catenin-independent function of LEF1 in early human myelopoiesis [XREF_BIBR]." + + + +
+ + + +
+ + + + + + 24378360 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The loss of E-cadherin results in the translocation of beta-catenin to the nucleus, where it activates beta-catenin-TCF and LEF -1 target genes and promotes the proliferation and metastasis of cancer." + + + +
+ + + +
+ + + + + + 29620261 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "By expressing a truncated form of β-catenin that inhibits Lef1, hair genes were ectopically expressed in epidermal cells that normally do not express them, resulting in epitheliod cysts resembling hair matrix tumors (pilomatircomas, cystic tumors of hair follicles found in humans)." + + + +
+ + + +
+ + + + + + 10456033 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to TOB1 inhibits LEF1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "This ventralized phenotype can also be achieved by overexpressing Tob1, which can bind beta-catenin and prevent the formation of beta, catenin, and LEF1 complex XREF_BIBR." + + + +
+ + + +
+ + + + + + 22574208 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ CTNNB1 bound to LEF1 inhibits LEF1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Furthermore, mammalian Dact1 inhibits the binding of Lef-1 with beta-catenin and promotes the interaction of Lef-1 with histone deacetylase (HDAC1) a co-repressor XREF_BIBR, XREF_BIBR." + + + +
+ + + +
+ + + + + + 23349981 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + + + + + + +
+
+
CTNNB1 decreases the amount of LEF1.
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 6 + + + + + + +
+
+
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 decreases the amount of LEF1. + + 5 / 5 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 5 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Although WT beta-catenin did not show an apparent effect compared with an empty vector, the mutant beta catenin induced Axin2 and repressed the expression of both Id2 and Lef1 in DN3 thymocytes (XREF_FIG), highlighting a specific effect mediated by beta-catenin activation." + + + +
+ + + +
+ + + + + + 23103132 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Knockdown of endogenous beta-catenin, however, decreased proliferation of oligodendrocytes by affecting expression of downstream lef1 and c-jun." + + + +
+ + + +
+ + + + + + 25178821 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Knockdown of AK045490 Promoted beta-Catenin Nuclear Translocation and Up-Regulates the Expression of TCF1, LEF1 and Runx2." + + + +
+ + + +
+ + + + + + 31835596 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Tcf3 directly represses transcription of Lef1, which is stimulated by Wnt and beta-catenin activity." + + + +
+ + + +
+ + + + + + 22573616 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Such N-terminally deleted beta-Catenin, lacking the first 86 and 89 amino acids (incrementN86 and incrementN89 beta-Catenin) was shown to cause increased LEF1 mediated transcription in vitro and increased proliferation, apoptosis and decreased migration in mouse intestinal epithelial cells XREF_BIBR, XREF_BIBR." + + + +
+ + + +
+ + + + + + 29872083 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ Modified CTNNB1 decreases the amount of LEF1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "This is in accordance with the decreased level of membranous beta-catenin that can transcriptionally activate LEF1 expression." + + + +
+ + + +
+ + + + + + 19781628 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + + + + + + +
+
+
CTNNB1 acetylates LEF1.
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 leads to the acetylation of LEF1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
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+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
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+ + + +
+ + + + + "Collectively, these results suggest that in early stages of cardiomyocyte differentiation Wnt and beta-catenin signaling promotes Isl1 expression via two ways : a novel TCF and LEF1 binding site and H3K9 acetylation conducted by CBP on the Isl1 promoter." + + + +
+ + + +
+ + + + + + 24610003 + + + + +
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+ + + +
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+ + + +
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+ + + + \ No newline at end of file diff --git a/notebooks/beta_catenin_dou/analysis_output/NOTUM_statements.html b/notebooks/beta_catenin_dou/analysis_output/NOTUM_statements.html new file mode 100644 index 000000000..f412a55de --- /dev/null +++ b/notebooks/beta_catenin_dou/analysis_output/NOTUM_statements.html @@ -0,0 +1,2297 @@ + + + + + + + + + + + + Statements for NOTUM + + + + + + + + + + + + + + + + + + + + + + + + + + +
+ + + + + + + +
+ + +
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+ Statements +

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CTNNB1 binds NOTUM.
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+ NOTUM binds CTNNB1. + + 2 / 2 + + +
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+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Notum overexpression was associated with intracellular β-catenin localization (100% of cases) and also observed in early lesions." + + + +
+ + + +
+ + + + + + 26517809 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "High levels of NOTUM protein were significantly associated with intracellular (nuclear or cytoplasmic) accumulation of beta-catenin protein: all 10 HCC with high intracellular beta-catenin also had high NOTUM expression, whereas only 2 of 30 cases (6.7%) without intracellular beta-catenin had high NOTUM expression (P < 0.00001)." + + + +
+ + + +
+ + + + + + 18429952 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + + + + + + +
+
+
CTNNB1 inhibits NOTUM.
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 inhibits NOTUM. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "The inhibition of β-catenin increases the effects of NOTUM on cell growth, cell transfer and osteogenic differentiation of BMSCs." + + + +
+ + + +
+ + + + + + 36465015 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + + + + + + +
+
+
CTNNB1 increases the amount of NOTUM.
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 increases the amount of NOTUM. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "These findings suggest that beta-catenin positively regulates NOTUM expression." + + + +
+ + + +
+ + + + + + 26974334 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + + + + + + +
+
+
CTNNB1 activates NOTUM.
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+ + + +
+
+ + + + + +
+
+
+ CTNNB1 activates NOTUM. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Notum is induced by Wnt and beta-catenin in developing trachea." + + + +
+ + + +
+ + + + + + 29428562 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + +
+
+
+
+
+ + + +
+
+ + + + \ No newline at end of file diff --git a/notebooks/beta_catenin_dou/analysis_output/TCF7L2_explanations.html b/notebooks/beta_catenin_dou/analysis_output/TCF7L2_explanations.html new file mode 100644 index 000000000..0ddc980c3 --- /dev/null +++ b/notebooks/beta_catenin_dou/analysis_output/TCF7L2_explanations.html @@ -0,0 +1,2603 @@ + + + + + + + + + + + + INDRA Results + + + + + + + + + + + + + + + + + + + + + + + + + + +
+ + + + + + + +
+ + +
+
+
+

+ Statements +

+
+
+ +
+
+ + + +
+ +
+ + + + databases + + + + + + psp + + + + + + cbn + + + + + + pc + + + + + + bel_lc + + + + + + signor + + + + + + biogrid + + + + + + tas + + + + + + hprd + + + + + + trrust + + + + + + ctd + + + + + + vhn + + + + + + pe + + + + + + drugbank + + + + + + omnipath + + + + + + conib + + + + + + crog + + + + + + dgi + + + + + + minerva + + + + + + creeds + + + + + + ubibrowser + + + + + + acsn + + + + + + + + | + +
| + + + + + + geneways + + + + + + tees + + + + + + gnbr + + + + + + semrep + + + + + + isi + + + + + + trips + + + + + + rlimsp + + + + + + medscan + + + + + + eidos + + + + + + sparser + + + + + + reach + + + + + reading + + + +
+
+ + + +
+
+ + + + + + + + +
+
+
+ + + +
+ + + + + + + + +
+ + + +
+
+ + + + + +
+
+
+ TCF7L2 binds LEF1. + + 7 / 7 + + +
+
+
+ + + + + + + + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + 4 + + + + + + 2 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "This was followed by an analysis of alternatively spliced forms of Lef1 and Tcf7l2 and their protein products in the embryonic and adult thalamus." + + + +
+ + + +
+ + + + + + 23152144 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "Therefore, Hif-3α2 probably binds to β-catenin, which in turn interacts with Tcf-4 and Lef1." + + + +
+ + + +
+ + + + + + 26765566 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "The CT of β-catenin is proteolytically sensitive and likely to be unfolded in the context of free β-catenin (Huber et al., 1997, 2001) or bound to Tcf-4 or Lef-1 (data not shown), which is the probable cause of the increase in observed size." + + + +
+ + + +
+ + + + + + 12408825 + + + + +
+
+
+ + + +
+
+
+
+ +
+ + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 24748645 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "As an example of this direct gene regulation by TCF7L2, the classic Wnt target genes Lef1 and Axin2 demonstrated early changes in gene expression following Tcf7l2 silencing, and were bound proximally by TCF7L2." + + + +
+ + + +
+ + + + + + 25414334 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ sparser + +
+ +
+
+ + + +
+ + + + + "During development β-catenin regulates transcription by forming a complex with TCF7L2 (also known as TCF4 ) or LEF1 [ xref ]." + + + +
+ + + +
+ + + + + + 24365576 + + + + +
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Comparing with set 3 (de novo), set 2 (switch) sites displayed stronger binding of Tcf7l2, Tcf7, Lef1, and beta-catenin, as well as higher level of markers of activated chromatin (ATAC-Seq and H3K27ac ChIP-Seq) in high CHIR condition (XREF_FIG)." + + + +
+ + + +
+ + + + + + 33587034 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ TCF7L2 increases the amount of LEF1. + + 2 / 2 + + +
+
+
+ + + + + + + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "On the other hand, downregulation of Tcf7l2 by shRNA knockdown in HL-1 cells enhanced the expression of Lef1, Tcf7, Cyclin D2, and Bmp4 (XREF_FIG.)" + + + +
+ + + +
+ + + + + + 30778164 + + + + +
+
+
+ + + +
+
+
+ + + + +
+ + + + + No evidence text available + + + +
+ + + +
+ + + + + + 12582159 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ TCF7L2 activates LEF1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "For example, Wnt cooperates with BMP and TGF-beta through co-occupancy of Smad target enhancers by Wnt activated lymphoid enhancer binding factor 1 (LEF1, also known as TCF1alpha) and transcription factor 7 like 2 (TCF7L2) transcription factors." + + + +
+ + + +
+ + + + + + 27449815 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ TCF7L2 activates DKK4. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Calcitriol also represses expression of DKK4 in SW480-ADH cells; DKK4 is induced by the TCF7L2 and CTNNB1 pathway and enhances the migratory, invasive and pro angiogenic potential of colorectal cancer." + + + +
+ + + +
+ + + + + + 27245104 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ TCF7L2 inhibits LEF1. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ reach + +
+ +
+
+ + + +
+ + + + + "Likewise, the focal expression of dominant negative TCF7L2 (dnTCF7L2, lacking β‐catenin binding domain) in the developing neocortex stimulated cell‐cycle exit in progenitors 63, confirming the role of nuclear β‐catenin and LEF1/TCFs in the regulation of neural progenitor pool size in the neocortex.Studies in which the uncommitted RG and committed IPs were analyzed as separate populations revealed opposite effects of canonical Wnt/β‐catenin signaling in each population (Fig. 3)." + + + +
+ + + +
+ + + + + + 31218672 + + + + +
+
+
+ + + +
+
+
+ + + + + +
+
+
+ TCF7L2 increases the amount of GLCE. + + 1 / 1 + + +
+
+
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + | + + + + + + + + + + + + + + + + + + + + 1 + + + + + + + + + + + + +
+
+
+
+
+ + + +
+
+
+
+
+ + +
+ medscan + +
+ +
+
+ + + +
+ + + + + "Furthermore, the ectopic expression of beta-catenin-TCF4 in cells that constitutively express low levels of the transactivation complex produces a significant increase of GLCE transcript level and, at the same time, enhances the rate of D-glucuronic acid epimerization in Heparan sulphate." + + + +
+ + + +
+ + + + + + 15853773 + + + + +
+
+
+ + + +
+
+
+ + + +
+
+
+
+ + + +
+
+
+
+
+ + + +
+
+ + + + \ No newline at end of file diff --git a/notebooks/beta_catenin_dou/analysis_output/go_results_discrete.csv b/notebooks/beta_catenin_dou/analysis_output/go_results_discrete.csv new file mode 100644 index 000000000..d2724c7b7 --- /dev/null +++ b/notebooks/beta_catenin_dou/analysis_output/go_results_discrete.csv @@ -0,0 +1,21 @@ +,curie,name,p,mlp,q,mlq +10407,go:0009987,cellular process,3.047003662099363e-08,7.516127023811921,0.00024042809778634176,3.619014779595691 +0,go:0005515,protein binding,8.67224819241658e-08,7.061868301486667,0.00024042809778634176,3.619014779595691 +3464,go:0044183,protein folding chaperone,8.67224819241658e-08,7.061868301486667,0.00024042809778634176,3.619014779595691 +11148,go:0140311,protein sequestering activity,8.67224819241658e-08,7.061868301486667,0.00024042809778634176,3.619014779595691 +4592,go:0006457,protein folding,8.838618402556495e-08,7.053615615873712,0.00024042809778634176,3.619014779595691 +628,go:0005509,calcium ion binding,3.293446323613209e-07,6.482349410269698,0.0007431276249053527,3.1289365940020484 +1622,go:0030178,negative regulation of Wnt signaling pathway,3.8246403752205497e-07,6.4174093946018305,0.0007431276249053527,3.1289365940020484 +812,go:0048306,calcium-dependent protein binding,4.941142351435279e-07,6.306172634159098,0.0008400559640233902,3.075691780537002 +1432,go:0012505,endomembrane system,2.164126459995871e-06,5.664717364973178,0.0032704759980448713,2.4853890337984637 +11907,go:0048731,system development,2.8126968196684943e-06,5.550877077874281,0.003825548944431119,2.417306237260242 +3290,go:0030111,regulation of Wnt signaling pathway,4.966888820533992e-06,5.303915561198453,0.005728784900281345,2.24193748397741 +365,go:0007275,multicellular organism development,5.0544385562367575e-06,5.296327078543825,0.005728784900281345,2.24193748397741 +760,go:0048856,anatomical structure development,1.6345213777411955e-05,4.786609394952488,0.017100865583583078,1.7669819066452852 +747,go:0090090,negative regulation of canonical Wnt signaling pathway,1.7853167640558282e-05,4.748284716987896,0.01734435236280237,1.7608419120520946 +436,go:0046872,metal ion binding,2.6677142597318348e-05,4.573860689773272,0.02418905443107512,1.6163811082149144 +4693,go:0032502,developmental process,3.586480656934232e-05,4.445331507114722,0.030487327134351556,1.5158806491566081 +12082,go:0043169,cation binding,4.465091624005425e-05,4.35016962492959,0.03397954432427526,1.4687824494451873 +68,go:0009966,regulation of signal transduction,4.707666895709805e-05,4.3271942744762475,0.03397954432427526,1.4687824494451873 +2226,go:0009968,negative regulation of signal transduction,4.7467931928625095e-05,4.3235996891063975,0.03397954432427526,1.4687824494451873 +3169,go:0046475,glycerophospholipid catabolic process,6.12329846806133e-05,4.213014571223601,0.041641491232051075,1.3804737262735427 diff --git a/notebooks/beta_catenin_dou/analysis_output/go_results_discrete.json b/notebooks/beta_catenin_dou/analysis_output/go_results_discrete.json new file mode 100644 index 000000000..e69de29bb diff --git a/notebooks/beta_catenin_dou/analysis_output/indra_downstream_results_discrete.csv b/notebooks/beta_catenin_dou/analysis_output/indra_downstream_results_discrete.csv new file mode 100644 index 000000000..40494247b --- /dev/null +++ b/notebooks/beta_catenin_dou/analysis_output/indra_downstream_results_discrete.csv @@ -0,0 +1,15 @@ +,curie,name,p,mlp,q,mlq +56,go:0030154,cell differentiation,3.9614915194701e-11,10.402141269448686,1.4088252290691515e-06,5.851142879678905 +430,go:0016477,cell migration,2.2628308483451025e-10,9.645347909313486,4.023652672984844e-06,5.3953795152076856 +58,go:0008283,cell population proliferation,1.0509538932877671e-07,6.978416336616793,0.001245835776899762,2.9045392015666742 +77,mesh:D009361,Neoplasm Invasiveness,7.91627912340161e-07,6.101478901224616,0.005957686240696306,2.224922372474168 +196,mesh:D009362,Neoplasm Metastasis,8.3762425002057e-07,6.07695075790793,0.005957686240696306,2.224922372474168 +11,go:0007165,signal transduction,2.01059468056165e-06,5.696675470794204,0.011917129770802325,1.923828331408067 +2052,hgnc:1071,BMP4,5.411398683341174e-06,5.2666904683596565,0.024865744178835004,1.6043985387271391 +20490,hgnc:11869,CEMIP2,5.593621275783259e-06,5.252306941504976,0.024865744178835004,1.6043985387271391 +435,go:0007155,cell adhesion,6.990844648323564e-06,5.155470348725729,0.026514908970620255,1.5765098595363738 +19410,hgnc:2411,CRYGD,7.4557570988443765e-06,5.127508249306155,0.026514908970620255,1.5765098595363738 +20474,hgnc:2510,CTNNA2,9.582882851926997e-06,5.018503820948346,0.03098146026027998,1.5088981163367896 +15298,hgnc:24709,VWA2,1.1974741701505678e-05,4.9217338456645985,0.035488144927553866,1.4499167019424422 +11145,hgnc:19185,FRAS1,1.4631076992057896e-05,4.834723704326327,0.04002499931296576,1.3976686668633829 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b/notebooks/beta_catenin_dou/analysis_output/reactome_results_discrete.csv new file mode 100644 index 000000000..2d61fc49f --- /dev/null +++ b/notebooks/beta_catenin_dou/analysis_output/reactome_results_discrete.csv @@ -0,0 +1,2 @@ +,curie,name,p,mlp,q,mlq +184,reactome:R-HSA-1483115,Hydrolysis of LPC,9.582882851926997e-06,5.018503820948346,0.02396679001266942,1.6203901292178433 diff --git a/notebooks/beta_catenin_dou/analysis_output/shared_families.txt b/notebooks/beta_catenin_dou/analysis_output/shared_families.txt new file mode 100644 index 000000000..4af18322e --- /dev/null +++ b/notebooks/beta_catenin_dou/analysis_output/shared_families.txt @@ -0,0 +1 @@ +None \ No newline at end of file diff --git a/notebooks/beta_catenin_dou/analysis_output/shared_go_terms.csv b/notebooks/beta_catenin_dou/analysis_output/shared_go_terms.csv new file mode 100644 index 000000000..60a9d1a71 --- /dev/null +++ b/notebooks/beta_catenin_dou/analysis_output/shared_go_terms.csv @@ -0,0 +1,15 @@ +"CURIE","Name","p-value","q-value" +"go:0005509","calcium ion binding","9.59e-09","1.32e-04" +"go:0005515","protein binding","3.18e-07","2.19e-03" +"go:0030178","negative regulation of Wnt signaling pathway","4.87e-07","2.24e-03" +"go:0048856","anatomical structure development","1.84e-06","5.74e-03" +"go:0046872","metal ion binding","2.08e-06","5.74e-03" +"go:0043169","cation binding","3.78e-06","8.62e-03" +"go:0032502","developmental process","4.37e-06","8.62e-03" +"go:0030111","regulation of Wnt signaling pathway","6.22e-06","1.07e-02" +"go:0043167","ion binding","1.04e-05","1.60e-02" +"go:0090090","negative regulation of canonical Wnt signaling pathway","2.09e-05","2.59e-02" +"go:0036094","small molecule binding","2.13e-05","2.59e-02" +"go:1990907","beta-catenin-TCF complex","2.25e-05","2.59e-02" +"go:0009966","regulation of signal transduction","3.77e-05","4.01e-02" + diff --git a/notebooks/beta_catenin_dou/analysis_output/shared_go_terms.png b/notebooks/beta_catenin_dou/analysis_output/shared_go_terms.png new file mode 100644 index 000000000..5a008b44b Binary files /dev/null and b/notebooks/beta_catenin_dou/analysis_output/shared_go_terms.png differ diff --git a/notebooks/beta_catenin_dou/analysis_output/shared_pathways.txt b/notebooks/beta_catenin_dou/analysis_output/shared_pathways.txt new file mode 100644 index 000000000..0da99ecf3 --- /dev/null +++ b/notebooks/beta_catenin_dou/analysis_output/shared_pathways.txt @@ -0,0 +1 @@ +[{'name': 'Pleural mesothelioma', 'id': 'WP5087'}, {'name': 'ncRNAs involved in Wnt signaling in hepatocellular carcinoma', 'id': 'WP4336'}, {'name': 'Wnt signaling', 'id': 'WP428'}, {'name': 'lncRNA in canonical Wnt signaling and colorectal cancer', 'id': 'WP4258'}, {'name': 'Signal Transduction', 'id': 'R-HSA-162582'}, {'name': 'Metabolism of proteins', 'id': 'R-HSA-392499'}, {'name': 'Alzheimer 39 s disease', 'id': 'WP5124'}, {'name': 'Pleural mesothelioma', 'id': 'WP5087'}, {'name': 'ncRNAs involved in Wnt signaling in hepatocellular carcinoma', 'id': 'WP4336'}, {'name': 'Wnt signaling', 'id': 'WP428'}, {'name': 'lncRNA in canonical Wnt signaling and colorectal cancer', 'id': 'WP4258'}, {'name': 'Extracellular vesicle mediated signaling in recipient cells', 'id': 'WP2870'}, {'name': 'Hair follicle development cytodifferentiation part 3 of 3', 'id': 'WP2840'}, {'name': 'Alzheimer 39 s disease and miRNA effects', 'id': 'WP2059'}, {'name': 'TCF dependent signaling in response to WNT', 'id': 'R-HSA-201681'}, {'name': 'Signaling by WNT', 'id': 'R-HSA-195721'}, {'name': 'Disease', 'id': 'R-HSA-1643685'}, {'name': 'Signal Transduction', 'id': 'R-HSA-162582'}, {'name': 'Diseases of signal transduction by growth factor receptors and second messengers', 'id': 'R-HSA-5663202'}, {'name': 'Signaling by WNT in cancer', 'id': 'R-HSA-4791275'}, {'name': 'Developmental Biology', 'id': 'R-HSA-1266738'}, {'name': 'Pleural mesothelioma', 'id': 'WP5087'}, {'name': 'Endometrial cancer', 'id': 'WP4155'}, {'name': 'Ectoderm differentiation', 'id': 'WP2858'}, {'name': 'Arrhythmogenic right ventricular cardiomyopathy', 'id': 'WP2118'}, {'name': 'Developmental Biology', 'id': 'R-HSA-1266738'}, {'name': 'Myogenesis', 'id': 'R-HSA-525793'}, {'name': 'TGF beta receptor signaling in skeletal dysplasias', 'id': 'WP4816'}, {'name': 'Disease', 'id': 'R-HSA-1643685'}, {'name': 'Metabolism of proteins', 'id': 'R-HSA-392499'}, {'name': 'Alzheimer 39 s disease', 'id': 'WP5124'}, {'name': 'Alzheimer 39 s disease and miRNA effects', 'id': 'WP2059'}, {'name': 'Pleural mesothelioma', 'id': 'WP5087'}, {'name': 'Hippo Merlin signaling dysregulation', 'id': 'WP4541'}, {'name': 'VEGFA VEGFR2 signaling', 'id': 'WP3888'}, {'name': 'Regulation of Expression and Function of Type II Classical Cadherins', 'id': 'R-HSA-9764260'}, {'name': 'Regulation of CDH11 function', 'id': 'R-HSA-9762292'}, {'name': 'Regulation of Homotypic Cell-Cell Adhesion', 'id': 'R-HSA-9759476'}, {'name': 'Regulation of CDH11 Expression and Function', 'id': 'R-HSA-9759475'}, {'name': 'Signal Transduction', 'id': 'R-HSA-162582'}, {'name': 'Cell-Cell communication', 'id': 'R-HSA-1500931'}, {'name': 'Cell junction organization', 'id': 'R-HSA-446728'}, {'name': 'Cell-cell junction organization', 'id': 'R-HSA-421270'}, {'name': 'Adherens junctions interactions', 'id': 'R-HSA-418990'}, {'name': 'VEGFA VEGFR2 signaling', 'id': 'WP3888'}, {'name': 'Signal Transduction', 'id': 'R-HSA-162582'}, {'name': 'Pleural mesothelioma', 'id': 'WP5087'}, {'name': 'Developmental Biology', 'id': 'R-HSA-1266738'}, {'name': 'DNA damage response only ATM dependent ', 'id': 'WP710'}, {'name': 'TGF beta receptor signaling', 'id': 'WP560'}, {'name': 'CKAP4 signaling pathway map', 'id': 'WP5322'}, {'name': 'Pleural mesothelioma', 'id': 'WP5087'}, {'name': 'Overlap between signal transduction pathways contributing to LMNA laminopathies', 'id': 'WP4879'}, {'name': 'Influence of laminopathies on Wnt signaling', 'id': 'WP4844'}, {'name': 'TGF beta receptor signaling in skeletal dysplasias', 'id': 'WP4816'}, {'name': 'Hippo signaling regulation pathways', 'id': 'WP4540'}, {'name': 'ncRNAs involved in Wnt signaling in hepatocellular carcinoma', 'id': 'WP4336'}, {'name': 'Wnt signaling', 'id': 'WP428'}, {'name': 'Breast cancer pathway', 'id': 'WP4262'}, {'name': 'lncRNA in canonical Wnt signaling and colorectal cancer', 'id': 'WP4258'}, {'name': 'Chromosomal and microsatellite instability in colorectal cancer ', 'id': 'WP4216'}, {'name': 'Endometrial cancer', 'id': 'WP4155'}, {'name': 'Wnt signaling pathway and pluripotency', 'id': 'WP399'}, {'name': 'Regulation of Wnt B catenin signaling by small molecule compounds', 'id': 'WP3664'}, {'name': 'Wnt beta catenin signaling pathway in leukemia', 'id': 'WP3658'}, {'name': 'Wnt signaling pathway', 'id': 'WP363'}, {'name': 'Endoderm differentiation', 'id': 'WP2853'}, {'name': 'Hair follicle development cytodifferentiation part 3 of 3', 'id': 'WP2840'}, {'name': 'Hair follicle development organogenesis part 2 of 3', 'id': 'WP2839'}, {'name': 'Arrhythmogenic right ventricular cardiomyopathy', 'id': 'WP2118'}, {'name': 'Generic Transcription Pathway', 'id': 'R-HSA-212436'}, {'name': 'Formation of the beta-catenin:TCF transactivating complex', 'id': 'R-HSA-201722'}, {'name': 'TCF dependent signaling in response to WNT', 'id': 'R-HSA-201681'}, {'name': 'Signaling by WNT', 'id': 'R-HSA-195721'}, {'name': 'Degradation of beta-catenin by the destruction complex', 'id': 'R-HSA-195253'}, {'name': 'RUNX3 regulates WNT signaling', 'id': 'R-HSA-8951430'}, {'name': 'Transcriptional regulation by RUNX3', 'id': 'R-HSA-8878159'}, {'name': 'Transcriptional Regulation by VENTX', 'id': 'R-HSA-8853884'}, {'name': 'Gene expression (Transcription)', 'id': 'R-HSA-74160'}, {'name': 'RNA Polymerase II Transcription', 'id': 'R-HSA-73857'}, {'name': 'Somitogenesis', 'id': 'R-HSA-9824272'}, {'name': 'Formation of axial mesoderm', 'id': 'R-HSA-9796292'}, {'name': 'Formation of paraxial mesoderm', 'id': 'R-HSA-9793380'}, {'name': 'Signal Transduction', 'id': 'R-HSA-162582'}, {'name': 'Gastrulation', 'id': 'R-HSA-9758941'}, {'name': 'Germ layer formation at gastrulation', 'id': 'R-HSA-9754189'}, {'name': 'Cardiogenesis', 'id': 'R-HSA-9733709'}, {'name': 'Developmental Biology', 'id': 'R-HSA-1266738'}, {'name': 'Binding of TCF/LEF:CTNNB1 to target gene promoters', 'id': 'R-HSA-4411364'}, {'name': 'Ca2+ pathway', 'id': 'R-HSA-4086398'}, {'name': 'Beta-catenin independent WNT signaling', 'id': 'R-HSA-3858494'}, {'name': 'Deactivation of the beta-catenin transactivating complex', 'id': 'R-HSA-3769402'}] \ No newline at end of file diff --git a/notebooks/beta_catenin_dou/analysis_output/shared_reactome.csv b/notebooks/beta_catenin_dou/analysis_output/shared_reactome.csv new file mode 100644 index 000000000..f7aaae8e2 --- /dev/null +++ b/notebooks/beta_catenin_dou/analysis_output/shared_reactome.csv @@ -0,0 +1,17 @@ +"CURIE","Name","p-value","q-value" +"reactome:R-HSA-4411364","Binding of TCF/LEF:CTNNB1 to target gene promoters","8.10e-06","9.12e-03" +"reactome:R-HSA-8951430","RUNX3 regulates WNT signaling","8.10e-06","9.12e-03" +"reactome:R-HSA-1483115","Hydrolysis of LPC","1.04e-05","9.12e-03" +"reactome:R-HSA-9762292","Regulation of CDH11 function","1.59e-05","1.04e-02" +"reactome:R-HSA-9796292","Formation of axial mesoderm","2.63e-05","1.38e-02" +"reactome:R-HSA-9754189","Germ layer formation at gastrulation","3.92e-05","1.72e-02" +"reactome:R-HSA-9733709","Cardiogenesis","1.01e-04","3.19e-02" +"reactome:R-HSA-9759475","Regulation of CDH11 Expression and Function","1.09e-04","3.19e-02" +"reactome:R-HSA-525793","Myogenesis","1.17e-04","3.19e-02" +"reactome:R-HSA-9764260","Regulation of Expression and Function of Type II Classical Cadherins","1.34e-04","3.19e-02" +"reactome:R-HSA-9759476","Regulation of Homotypic Cell-Cell Adhesion","1.34e-04","3.19e-02" +"reactome:R-HSA-4791275","Signaling by WNT in cancer","1.61e-04","3.52e-02" +"reactome:R-HSA-201681","TCF dependent signaling in response to WNT","1.82e-04","3.68e-02" +"reactome:R-HSA-8853884","Transcriptional Regulation by VENTX","2.12e-04","3.98e-02" +"reactome:R-HSA-3769402","Deactivation of the beta-catenin transactivating complex","2.46e-04","4.31e-02" + diff --git a/notebooks/beta_catenin_dou/analysis_output/shared_upstream.csv b/notebooks/beta_catenin_dou/analysis_output/shared_upstream.csv new file mode 100644 index 000000000..096533fc2 --- /dev/null +++ b/notebooks/beta_catenin_dou/analysis_output/shared_upstream.csv @@ -0,0 +1,195 @@ +"CURIE","Name","p-value","q-value" +"chebi:33216","bisphenol A","1.04e-11","5.10e-07" +"chebi:39867","valproic acid","1.42e-09","3.47e-05" +"chebi:28119","2,3,7,8-tetrachlorodibenzodioxine","4.18e-09","6.83e-05" +"chebi:16469","17beta-estradiol","7.14e-09","8.75e-05" +"chebi:27470","folic acid","9.73e-09","9.54e-05" +"hgnc:6551","LEF1","1.54e-08","1.26e-04" +"mesh:C459179","4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide","6.56e-08","4.59e-04" +"chebi:34372","4,4'-sulfonyldiphenol","8.96e-08","4.96e-04" +"chebi:15354","choline","9.10e-08","4.96e-04" +"chebi:78510","dorsomorphin","1.40e-07","6.84e-04" +"chebi:46024","trichostatin A","2.09e-07","9.29e-04" +"chebi:35549","perfluorooctanoic acid","2.64e-07","1.08e-03" +"chebi:42588","4-hydroxyphenyl retinamide","5.08e-07","1.82e-03" +"chebi:15379","dioxygen","5.21e-07","1.82e-03" +"hgnc:27106","NOTUM","7.91e-07","2.58e-03" +"hgnc:3157","EDA","8.42e-07","2.58e-03" +"hgnc:7611","MYOD1","9.50e-07","2.74e-03" +"chebi:32506","4,4'-diaminodiphenylmethane","1.03e-06","2.80e-03" +"chebi:15640","5-formyltetrahydrofolic acid","1.13e-06","2.90e-03" +"chebi:2504","aflatoxin B1","1.23e-06","3.01e-03" +"chebi:17823","calcitriol","1.52e-06","3.46e-03" +"chebi:28748","doxorubicin","1.55e-06","3.46e-03" +"hgnc:13829","WNT10A","1.66e-06","3.54e-03" +"hgnc:9235","PPARD","1.86e-06","3.79e-03" +"chebi:4031","cyclosporin A","2.03e-06","3.95e-03" +"chebi:17234","glucose","2.10e-06","3.95e-03" +"hgnc:10848","SHH","2.29e-06","4.11e-03" +"hgnc:6698","LRP6","2.35e-06","4.11e-03" +"chebi:32509","pirinixic acid","2.56e-06","4.32e-03" +"chebi:15367","all-trans-retinoic acid","2.65e-06","4.32e-03" +"hgnc:3676","FGF2","2.89e-06","4.44e-03" +"mesh:C575430","FH535","2.90e-06","4.44e-03" +"hgnc:583","APC","2.99e-06","4.44e-03" +"chebi:34317","3,3',4,4',5-pentachlorobiphenyl","3.26e-06","4.70e-03" +"hgnc:1071","BMP4","3.55e-06","4.81e-03" +"chebi:73755","1,2-dimethylhydrazine","3.59e-06","4.81e-03" +"hgnc:11641","TCF7L2","3.71e-06","4.81e-03" +"chebi:45716","vorinostat","3.73e-06","4.81e-03" +"hgnc:20175","GOLT1B","4.34e-06","5.32e-03" +"hgnc:13618","FBXO16","4.34e-06","5.32e-03" +"chebi:16643","L-methionine","4.62e-06","5.46e-03" +"mesh:C548651","2-(1'H-indole-3'-carbonyl)thiazole-4-carboxylic acid methyl ester","4.77e-06","5.46e-03" +"chebi:34202","2,2',4,4',5,5'-hexachlorobiphenyl","4.79e-06","5.46e-03" +"hgnc:11769","TGFB3","5.08e-06","5.65e-03" +"chebi:28216","methylmercury chloride","5.22e-06","5.68e-03" +"chebi:62878","XAV939","5.43e-06","5.78e-03" +"hgnc:17652","PORCN","6.26e-06","6.53e-03" +"mesh:D001335","Vehicle Emissions","7.04e-06","7.09e-03" +"chebi:27385","tetrachloromethane","7.32e-06","7.09e-03" +"hgnc:5102","HOXA13","7.50e-06","7.09e-03" +"hgnc:2916","DLX3","7.50e-06","7.09e-03" +"fplx:CSNK1","CSNK1","7.54e-06","7.09e-03" +"hgnc:1833","CEBPA","7.98e-06","7.09e-03" +"hgnc:33843","NRARP","8.10e-06","7.09e-03" +"hgnc:2510","CTNNA2","8.10e-06","7.09e-03" +"chebi:69774","loliolide","8.10e-06","7.09e-03" +"chebi:29865","benzo[a]pyrene","8.51e-06","7.31e-03" +"fplx:TCF_LEF","TCF_LEF","8.91e-06","7.52e-03" +"hgnc:16265","WNT5B","9.65e-06","7.90e-03" +"mesh:D014028","Tobacco Smoke Pollution","9.67e-06","7.90e-03" +"chebi:41879","dexamethasone","1.03e-05","8.10e-03" +"chebi:77145","ginsenoside F2","1.04e-05","8.10e-03" +"hgnc:23244","RBM25","1.04e-05","8.10e-03" +"chebi:16236","ethanol","1.24e-05","9.47e-03" +"mesh:C511295","2,2',4,4'-tetrabromodiphenyl ether","1.42e-05","1.07e-02" +"hgnc:4602","CXCL1","1.45e-05","1.08e-02" +"chebi:34342","3-methylcholanthrene","1.54e-05","1.08e-02" +"chebi:8416","Pristimerin","1.56e-05","1.08e-02" +"mesh:D011125","Adenomatous Polyposis Coli","1.59e-05","1.08e-02" +"hgnc:11838","TLE2","1.59e-05","1.08e-02" +"hgnc:10576","CLEC11A","1.59e-05","1.08e-02" +"hgnc:16717","DHX32","1.59e-05","1.08e-02" +"hgnc:2891","DKK1","1.62e-05","1.09e-02" +"chebi:50859","bexarotene","1.65e-05","1.09e-02" +"hgnc:9451","PROC","1.70e-05","1.11e-02" +"chebi:17606","diiodine","1.74e-05","1.12e-02" +"hgnc:7391","MSX1","1.77e-05","1.13e-02" +"hgnc:25529","WDR74","1.91e-05","1.18e-02" +"mesh:C417520","3-(3-chloro-4-hydroxyphenylamino)-4-(4-nitrophenyl)-1H-pyrrole-2,5-dione","1.91e-05","1.18e-02" +"hgnc:8910","PGR","1.95e-05","1.19e-02" +"chebi:34674","dextran sulfate","2.01e-05","1.21e-02" +"hgnc:6059","IDO1","2.02e-05","1.21e-02" +"fplx:MEK","MEK","2.23e-05","1.31e-02" +"hgnc:407","ALDH1B1","2.25e-05","1.31e-02" +"mesh:D011225","Pre-Eclampsia","2.27e-05","1.31e-02" +"fplx:Wnt","Wnt","2.49e-05","1.42e-02" +"chebi:27684","phenylmercury acetate","2.55e-05","1.43e-02" +"hgnc:21214","ADTRP","2.63e-05","1.46e-02" +"hgnc:3236","EGFR","2.92e-05","1.61e-02" +"hgnc:12872","ZIC1","3.20e-05","1.74e-02" +"hgnc:2514","CTNNB1","3.31e-05","1.78e-02" +"hgnc:13520","MESD","3.46e-05","1.81e-02" +"chebi:6888","6alpha-methylprednisolone","3.47e-05","1.81e-02" +"chebi:37537","phorbol 13-acetate 12-myristate","3.48e-05","1.81e-02" +"hgnc:2894","DKK4","3.92e-05","2.02e-02" +"chebi:8502","6-propyl-2-thiouracil","4.04e-05","2.06e-02" +"hgnc:13771","SOST","4.35e-05","2.20e-02" +"chebi:50594","carbon nanotube","4.42e-05","2.20e-02" +"fplx:Notch","Notch","4.48e-05","2.20e-02" +"chebi:90695","anthra[1,9-cd]pyrazol-6(2H)-one","4.53e-05","2.20e-02" +"hgnc:11634","TCF4","4.53e-05","2.20e-02" +"hgnc:12769","CCN4","4.78e-05","2.30e-02" +"hgnc:21259","CAPRIN2","4.93e-05","2.35e-02" +"chebi:27732","caffeine","5.30e-05","2.50e-02" +"hgnc:10472","RUNX2","5.47e-05","2.53e-02" +"hgnc:6515","LATS2","5.48e-05","2.53e-02" +"chebi:3638","chloroquine","5.54e-05","2.54e-02" +"fplx:BMP","BMP","5.85e-05","2.60e-02" +"hgnc:6553","LEP","5.88e-05","2.60e-02" +"chebi:41922","diethylstilbestrol","5.91e-05","2.60e-02" +"hgnc:7400","MT1H","6.05e-05","2.60e-02" +"hgnc:6867","MAP4K5","6.05e-05","2.60e-02" +"hgnc:11192","SOX13","6.05e-05","2.60e-02" +"hgnc:21231","DACT2","6.05e-05","2.60e-02" +"hgnc:9236","PPARG","6.19e-05","2.64e-02" +"mesh:D052638","Particulate Matter","6.62e-05","2.76e-02" +"chebi:79989","GW 6471","6.65e-05","2.76e-02" +"hgnc:2592","CYP11B2","6.65e-05","2.76e-02" +"chebi:4903","17alpha-ethynylestradiol","7.23e-05","2.95e-02" +"hgnc:23589","ZNF503","7.29e-05","2.95e-02" +"hgnc:17765","RNF138","7.29e-05","2.95e-02" +"chebi:4026","cyclophosphamide hydrate","7.41e-05","2.97e-02" +"hgnc:2500","CCN2","7.77e-05","3.02e-02" +"mesh:C112772","ginsenoside M1","7.82e-05","3.02e-02" +"hgnc:12000","TP53BP2","7.82e-05","3.02e-02" +"chebi:8653","pyocyanine","7.94e-05","3.02e-02" +"hgnc:17849","ADGRA2","7.94e-05","3.02e-02" +"chebi:133343","beta-D-glucosamine 6-sulfate","7.94e-05","3.02e-02" +"chebi:80852","Morroniside","7.94e-05","3.02e-02" +"chebi:17026","progesterone","8.48e-05","3.18e-02" +"hgnc:14402","HIPK2","8.61e-05","3.18e-02" +"chebi:31941","oxaliplatin","8.62e-05","3.18e-02" +"chebi:6942","minoxidil","8.63e-05","3.18e-02" +"hgnc:57","ABCC6","8.94e-05","3.26e-02" +"fplx:VEGF","VEGF","8.97e-05","3.26e-02" +"hgnc:16910","CPQ","9.35e-05","3.34e-02" +"hgnc:11990","TOP2B","9.35e-05","3.34e-02" +"hgnc:11633","TCF3","9.84e-05","3.49e-02" +"go:0031099","regeneration","1.01e-04","3.51e-02" +"hgnc:18040","ARID1B","1.01e-04","3.51e-02" +"mesh:D000072283","A549 Cells","1.01e-04","3.51e-02" +"hgnc:9692","PTX3","1.02e-04","3.51e-02" +"chebi:47807","sulforaphane","1.04e-04","3.57e-02" +"hgnc:29608","MTDH","1.07e-04","3.63e-02" +"chebi:22977","cadmium atom","1.07e-04","3.63e-02" +"hgnc:34","ABCA4","1.09e-04","3.65e-02" +"hgnc:8861","PF4","1.11e-04","3.70e-02" +"chebi:2979","baicalein","1.12e-04","3.71e-02" +"hgnc:9449","PRNP","1.13e-04","3.72e-02" +"hgnc:4232","GDNF","1.15e-04","3.76e-02" +"go:0016055","Wnt signaling pathway","1.17e-04","3.76e-02" +"hgnc:28106","TMEM97","1.17e-04","3.76e-02" +"hgnc:1806","CDX2","1.21e-04","3.87e-02" +"hgnc:8528","OXT","1.24e-04","3.92e-02" +"hgnc:12591","UROD","1.25e-04","3.92e-02" +"hgnc:3223","EFNA3","1.25e-04","3.92e-02" +"hgnc:11621","HNF1A","1.27e-04","3.94e-02" +"fplx:IKB","IKB","1.27e-04","3.94e-02" +"hgnc:19196","SP8","1.34e-04","4.06e-02" +"hgnc:3222","EFNA2","1.34e-04","4.06e-02" +"hgnc:21336","RNF146","1.34e-04","4.06e-02" +"hgnc:20001","PCSK9","1.36e-04","4.10e-02" +"mesh:D000073878","Palm Oil","1.36e-04","4.10e-02" +"hgnc:28210","FAM83A","1.42e-04","4.23e-02" +"hgnc:8623","PAX9","1.42e-04","4.23e-02" +"mesh:C028474","1,4-bis(2-(3,5-dichloropyridyloxy))benzene","1.52e-04","4.36e-02" +"hgnc:7137","AFDN","1.52e-04","4.36e-02" +"mesh:C014148","phosphocitrate","1.52e-04","4.36e-02" +"mesh:C538809","sodium pentaborate","1.52e-04","4.36e-02" +"hgnc:6696","LRP4","1.52e-04","4.36e-02" +"hgnc:30257","PYGO2","1.52e-04","4.36e-02" +"chebi:132233","1-phenylpropan-2-amine","1.54e-04","4.38e-02" +"hgnc:3394","EPHB3","1.61e-04","4.52e-02" +"hgnc:16267","WNT16","1.61e-04","4.52e-02" +"hgnc:7776","NFATC2","1.61e-04","4.52e-02" +"hgnc:11190","SOX10","1.69e-04","4.68e-02" +"chebi:50131","5-aza-2'-deoxycytidine","1.70e-04","4.68e-02" +"hgnc:7978","NR3C1","1.71e-04","4.68e-02" +"chebi:29678","sodium arsenite","1.73e-04","4.68e-02" +"chebi:27789","1,2-dichloroethane","1.74e-04","4.68e-02" +"chebi:4791","endosulfan","1.75e-04","4.68e-02" +"fplx:JAK","JAK","1.79e-04","4.68e-02" +"hgnc:7963","NR1D2","1.81e-04","4.68e-02" +"chebi:71554","PPARgamma agonist","1.81e-04","4.68e-02" +"chebi:35581","indole","1.81e-04","4.68e-02" +"hgnc:3973","FSTL3","1.81e-04","4.68e-02" +"hgnc:26727","ERFE","1.81e-04","4.68e-02" +"hgnc:17748","DACT1","1.81e-04","4.68e-02" +"hgnc:12779","WNT9B","1.81e-04","4.68e-02" +"chebi:6498","lipoxin A4","1.87e-04","4.83e-02" +"hgnc:20351","OTUB2","1.91e-04","4.85e-02" +"hgnc:15520","LPAR6","1.91e-04","4.85e-02" +"hgnc:10967","SLC22A3","1.91e-04","4.85e-02" + diff --git a/notebooks/beta_catenin_dou/analysis_output/shared_wikipathways.csv b/notebooks/beta_catenin_dou/analysis_output/shared_wikipathways.csv new file mode 100644 index 000000000..4252d096a --- /dev/null +++ b/notebooks/beta_catenin_dou/analysis_output/shared_wikipathways.csv @@ -0,0 +1,27 @@ +"CURIE","Name","p-value","q-value" +"wikipathways:WP5087","Pleural mesothelioma","3.03e-09","2.56e-06" +"wikipathways:WP4336","ncRNAs involved in Wnt signaling in hepatocellular carcinoma","1.60e-07","6.70e-05" +"wikipathways:WP4258","lncRNA in canonical Wnt signaling and colorectal cancer","2.37e-07","6.70e-05" +"wikipathways:WP428","Wnt signaling","4.39e-07","9.28e-05" +"wikipathways:WP4816","TGF beta receptor signaling in skeletal dysplasias","4.67e-06","7.90e-04" +"wikipathways:WP4155","Endometrial cancer","5.70e-06","8.03e-04" +"wikipathways:WP2118","Arrhythmogenic right ventricular cardiomyopathy","9.26e-06","1.12e-03" +"wikipathways:WP2840","Hair follicle development cytodifferentiation part 3 of 3","1.51e-05","1.59e-03" +"wikipathways:WP3664","Regulation of Wnt B catenin signaling by small molecule compounds","3.92e-05","3.69e-03" +"wikipathways:WP5061","Fatty acid transporters","4.41e-05","3.73e-03" +"wikipathways:WP3658","Wnt beta catenin signaling pathway in leukemia","9.35e-05","7.19e-03" +"wikipathways:WP2870","Extracellular vesicle mediated signaling in recipient cells","1.25e-04","8.81e-03" +"wikipathways:WP2839","Hair follicle development organogenesis part 2 of 3","1.42e-04","9.27e-03" +"wikipathways:WP5323","Fatty Acids and Lipoproteins Transport in Hepatocytes","1.71e-04","1.03e-02" +"wikipathways:WP4844","Influence of laminopathies on Wnt signaling","1.91e-04","1.08e-02" +"wikipathways:WP363","Wnt signaling pathway","3.09e-04","1.63e-02" +"wikipathways:WP5124","Alzheimer 39 s disease","3.91e-04","1.88e-02" +"wikipathways:WP2059","Alzheimer 39 s disease and miRNA effects","4.13e-04","1.88e-02" +"wikipathways:WP560","TGF beta receptor signaling","4.23e-04","1.88e-02" +"wikipathways:WP4879","Overlap between signal transduction pathways contributing to LMNA laminopathies","4.54e-04","1.92e-02" +"wikipathways:WP4400","FABP4 in ovarian cancer","5.50e-04","2.21e-02" +"wikipathways:WP3942","PPAR signaling pathway","6.27e-04","2.41e-02" +"wikipathways:WP4216","Chromosomal and microsatellite instability in colorectal cancer","7.44e-04","2.74e-02" +"wikipathways:WP4540","Hippo signaling regulation pathways","1.33e-03","4.70e-02" +"wikipathways:WP399","Wnt signaling pathway and pluripotency","1.42e-03","4.79e-02" + diff --git a/notebooks/beta_catenin_dou/analysis_output/wikipathways_results_discrete.csv b/notebooks/beta_catenin_dou/analysis_output/wikipathways_results_discrete.csv new file mode 100644 index 000000000..498ee9923 --- /dev/null +++ b/notebooks/beta_catenin_dou/analysis_output/wikipathways_results_discrete.csv @@ -0,0 +1,6 @@ +,curie,name,p,mlp,q,mlq +621,wikipathways:WP5087,Malignant pleural mesothelioma,7.814249661698205e-08,7.107112717379757,5.477789012850442e-05,4.261394699413098 +409,wikipathways:WP4336,ncRNAs involved in Wnt signaling in hepatocellular carcinoma,1.47099024589903e-05,4.832390207059195,0.005151050587842225,2.288104184945116 +381,wikipathways:WP4258,lncRNA in canonical Wnt signaling and colorectal cancer,2.2044439034988128e-05,4.656700948192112,0.005151050587842225,2.288104184945116 +387,wikipathways:WP428,Wnt signaling,3.2268403782087996e-05,4.4912225172665865,0.005655037762810921,2.24756449062789 +611,wikipathways:WP5061,Fatty acid transporters,4.06092426416951e-05,4.391375109982993,0.0056934158183656524,2.2446270963523536 diff --git a/notebooks/beta_catenin_dou/beta_catenin_dou.ipynb b/notebooks/beta_catenin_dou/beta_catenin_dou.ipynb index a35fc5f44..a1ec00a66 100644 --- a/notebooks/beta_catenin_dou/beta_catenin_dou.ipynb +++ b/notebooks/beta_catenin_dou/beta_catenin_dou.ipynb @@ -12,8 +12,8 @@ "name": "stderr", "output_type": "stream", "text": [ - "INFO: [2024-08-09 16:02:52] numexpr.utils - NumExpr defaulting to 10 threads.\n", - "WARNING: [2024-08-09 16:02:55] indra_cogex.apps.constants - Pusher app not configured. Please set the environment variables CLARE_PUSHER_APP_ID, CLARE_PUSHER_KEY, CLARE_PUSHER_SECRET, and CLARE_PUSHER_CLUSTER.\n" + "INFO: [2024-08-09 16:09:08] numexpr.utils - NumExpr defaulting to 10 threads.\n", + "WARNING: [2024-08-09 16:09:11] indra_cogex.apps.constants - Pusher app not configured. Please set the environment variables CLARE_PUSHER_APP_ID, CLARE_PUSHER_KEY, CLARE_PUSHER_SECRET, and CLARE_PUSHER_CLUSTER.\n" ] } ], @@ -32,7 +32,7 @@ " 'CXCL14', 'PLA2G4A', 'RCN2', 'TTC9', 'FABP4', 'GPCPD1', 'VSNL1',\n", " 'CRYBB1', 'LEF1', 'PDZD8', 'FNDC3A']\n", "\n", - "output_folder = 'analysis_test'" + "output_folder = 'analysis_output'" ] }, { @@ -47,7 +47,7 @@ "name": "stderr", "output_type": "stream", "text": [ - "INFO: [2024-08-09 16:03:18] indra_cogex.analysis.protein_analysis - Dataframe of protiens that have INDRA relationships with source that have been filtered:\n", + "INFO: [2024-08-09 16:09:34] indra_cogex.analysis.protein_analysis - Dataframe of protiens that have INDRA relationships with source that have been filtered:\n", " name stmt_json target_type \\\n", "2490 LEF1 {\"type\": \"Complex\", \"members\": [{\"name\": \"tcf7... HGNC \n", "2491 LEF1 {\"type\": \"Complex\", \"members\": [{\"name\": \"CTNN... HGNC \n", @@ -88,35 +88,35 @@ "6370 [Evidence(source_api='reach',\\n pmid='... \n", "\n", "[86 rows x 8 columns]\n", - "INFO: [2024-08-09 16:03:18] indra.sources.indra_db_rest.util - query: https://db.indra.bio/curation/list\n", - "INFO: [2024-08-09 16:03:18] indra.sources.indra_db_rest.util - params: {'api_key': '[api-key]'}\n", - "INFO: [2024-08-09 16:03:18] indra.sources.indra_db_rest.util - data: None\n", - "INFO: [2024-08-09 16:03:24] indra.tools.assemble_corpus - Filtering 67 statements with any incorrect curations...\n", - "INFO: [2024-08-09 16:03:24] indra.tools.assemble_corpus - 67 statements after filter...\n", - "INFO: [2024-08-09 16:03:24] indra.tools.assemble_corpus - Filtering 4 statements with any incorrect curations...\n", - "INFO: [2024-08-09 16:03:24] indra.tools.assemble_corpus - 1 statements after filter...\n", - "INFO: [2024-08-09 16:03:24] indra.tools.assemble_corpus - Filtering 4 statements with any incorrect curations...\n", - "INFO: [2024-08-09 16:03:24] indra.tools.assemble_corpus - 4 statements after filter...\n", - "INFO: [2024-08-09 16:03:24] indra.tools.assemble_corpus - Filtering 4 statements with any incorrect curations...\n", - "INFO: [2024-08-09 16:03:24] indra.tools.assemble_corpus - 4 statements after filter...\n", - "INFO: [2024-08-09 16:03:24] indra.tools.assemble_corpus - Filtering 1 statements with any incorrect curations...\n", - "INFO: [2024-08-09 16:03:24] indra.tools.assemble_corpus - 1 statements after filter...\n", - "INFO: [2024-08-09 16:03:24] indra.tools.assemble_corpus - Filtering 2 statements with any incorrect curations...\n", - "INFO: [2024-08-09 16:03:24] indra.tools.assemble_corpus - 2 statements after filter...\n", - "INFO: [2024-08-09 16:03:24] indra.tools.assemble_corpus - Filtering 2 statements with any incorrect curations...\n", - "INFO: [2024-08-09 16:03:24] indra.tools.assemble_corpus - 1 statements after filter...\n", - "INFO: [2024-08-09 16:03:24] indra.tools.assemble_corpus - Filtering 1 statements with any incorrect curations...\n", - "INFO: [2024-08-09 16:03:24] indra.tools.assemble_corpus - 1 statements after filter...\n", - "INFO: [2024-08-09 16:03:24] indra.tools.assemble_corpus - Filtering 1 statements with any incorrect curations...\n", - "INFO: [2024-08-09 16:03:24] indra.tools.assemble_corpus - 1 statements after filter...\n", - "INFO: [2024-08-09 16:03:24] indra_cogex.client.enrichment.utils - Loading /Users/ben/.data/indra/cogex/app_cache/go.pkl\n", - "INFO: [2024-08-09 16:03:25] indra_cogex.client.enrichment.utils - Loading /Users/ben/.data/indra/cogex/app_cache/wiki.pkl\n", - "INFO: [2024-08-09 16:03:25] indra_cogex.client.enrichment.utils - Loading /Users/ben/.data/indra/cogex/app_cache/reactome.pkl\n", - "INFO: [2024-08-09 16:03:25] indra_cogex.client.enrichment.utils - Loading /Users/ben/.data/indra/cogex/app_cache/hpo.pkl\n", - "INFO: [2024-08-09 16:03:26] indra_cogex.client.enrichment.utils - Loading /Users/ben/.data/indra/cogex/app_cache/to_targets.pkl\n", - "INFO: [2024-08-09 16:03:28] indra_cogex.client.enrichment.utils - Loading /Users/ben/.data/indra/cogex/app_cache/to_regs.pkl\n", - "INFO: [2024-08-09 16:03:36] indra_cogex.analysis.protein_analysis - There are no shared protein family complexes\n", - "INFO: [2024-08-09 16:03:37] indra_cogex.analysis.protein_analysis - These are the shared upstream bioentities between thegene list and source_protein\n", + "INFO: [2024-08-09 16:09:34] indra.sources.indra_db_rest.util - query: https://db.indra.bio/curation/list\n", + "INFO: [2024-08-09 16:09:34] indra.sources.indra_db_rest.util - params: {'api_key': '[api-key]'}\n", + "INFO: [2024-08-09 16:09:34] indra.sources.indra_db_rest.util - data: None\n", + "INFO: [2024-08-09 16:09:40] indra.tools.assemble_corpus - Filtering 67 statements with any incorrect curations...\n", + "INFO: [2024-08-09 16:09:40] indra.tools.assemble_corpus - 67 statements after filter...\n", + "INFO: [2024-08-09 16:09:40] indra.tools.assemble_corpus - Filtering 4 statements with any incorrect curations...\n", + "INFO: [2024-08-09 16:09:40] indra.tools.assemble_corpus - 1 statements after filter...\n", + "INFO: [2024-08-09 16:09:40] indra.tools.assemble_corpus - Filtering 4 statements with any incorrect curations...\n", + "INFO: [2024-08-09 16:09:40] indra.tools.assemble_corpus - 4 statements after filter...\n", + "INFO: [2024-08-09 16:09:40] indra.tools.assemble_corpus - Filtering 4 statements with any incorrect curations...\n", + "INFO: [2024-08-09 16:09:40] indra.tools.assemble_corpus - 4 statements after filter...\n", + "INFO: [2024-08-09 16:09:40] indra.tools.assemble_corpus - Filtering 1 statements with any incorrect curations...\n", + "INFO: [2024-08-09 16:09:40] indra.tools.assemble_corpus - 1 statements after filter...\n", + "INFO: [2024-08-09 16:09:40] indra.tools.assemble_corpus - Filtering 2 statements with any incorrect curations...\n", + "INFO: [2024-08-09 16:09:40] indra.tools.assemble_corpus - 2 statements after filter...\n", + "INFO: [2024-08-09 16:09:40] indra.tools.assemble_corpus - Filtering 2 statements with any incorrect curations...\n", + "INFO: [2024-08-09 16:09:40] indra.tools.assemble_corpus - 1 statements after filter...\n", + "INFO: [2024-08-09 16:09:40] indra.tools.assemble_corpus - Filtering 1 statements with any incorrect curations...\n", + "INFO: [2024-08-09 16:09:40] indra.tools.assemble_corpus - 1 statements after filter...\n", + "INFO: [2024-08-09 16:09:40] indra.tools.assemble_corpus - Filtering 1 statements with any incorrect curations...\n", + "INFO: [2024-08-09 16:09:40] indra.tools.assemble_corpus - 1 statements after filter...\n", + "INFO: [2024-08-09 16:09:41] indra_cogex.client.enrichment.utils - Loading /Users/ben/.data/indra/cogex/app_cache/go.pkl\n", + "INFO: [2024-08-09 16:09:41] indra_cogex.client.enrichment.utils - Loading /Users/ben/.data/indra/cogex/app_cache/wiki.pkl\n", + "INFO: [2024-08-09 16:09:41] indra_cogex.client.enrichment.utils - Loading /Users/ben/.data/indra/cogex/app_cache/reactome.pkl\n", + "INFO: [2024-08-09 16:09:41] indra_cogex.client.enrichment.utils - Loading /Users/ben/.data/indra/cogex/app_cache/hpo.pkl\n", + "INFO: [2024-08-09 16:09:42] indra_cogex.client.enrichment.utils - Loading /Users/ben/.data/indra/cogex/app_cache/to_targets.pkl\n", + "INFO: [2024-08-09 16:09:44] indra_cogex.client.enrichment.utils - Loading /Users/ben/.data/indra/cogex/app_cache/to_regs.pkl\n", + "INFO: [2024-08-09 16:09:53] indra_cogex.analysis.protein_analysis - There are no shared protein family complexes\n", + "INFO: [2024-08-09 16:09:53] indra_cogex.analysis.protein_analysis - These are the shared upstream bioentities between thegene list and source_protein\n", " curie name p mlp \\\n", "48 chebi:33216 bisphenol A 2.184537e-11 10.660641 \n", "90 chebi:39867 valproic acid 2.783294e-09 8.555441 \n", @@ -148,7 +148,7 @@ "866 1.838673e-02 1.735496 \n", "63 1.866556e-02 1.728959 \n", "50 3.667266e-02 1.435658 \n", - "INFO: [2024-08-09 16:03:37] indra_cogex.analysis.protein_analysis - These are shared complexes between the gene list and the source_protein\n", + "INFO: [2024-08-09 16:09:53] indra_cogex.analysis.protein_analysis - These are shared complexes between the gene list and the source_protein\n", " curie name p mlp q mlq\n", "0 go:0005515 protein binding 8.672248e-08 7.061868 0.00024 3.619015\n" ] @@ -175,34 +175,32 @@ } ], "source": [ - "explain_downstream(source_protein_name, target_protein_names, 'analysis_test')" + "explain_downstream(source_protein_name, target_protein_names, output_folder)" ] }, { - "cell_type": "code", - "execution_count": 3, - "id": "e9715d48", + "cell_type": "markdown", + "id": "3cce6c8e", "metadata": {}, - "outputs": [], "source": [ - "htmls = glob.glob(os.path.join(output_folder, '*.html'))\n", - "for html in htmls:\n", - " HTML(html)" + "Look into explaining some upstreams through specific statements" ] }, { "cell_type": "code", - "execution_count": 4, + "execution_count": 3, "id": "fc12f155", "metadata": {}, "outputs": [], "source": [ - "from indra.sources import indra_db_rest" + "from indra.sources import indra_db_rest\n", + "from indra.tools import assemble_corpus as ac\n", + "from indra.assemblers.html import HtmlAssembler" ] }, { "cell_type": "code", - "execution_count": 5, + "execution_count": 4, "id": "ced312de", "metadata": {}, "outputs": [ @@ -210,186 +208,57 @@ "name": "stderr", "output_type": "stream", "text": [ - "INFO: [2024-08-09 16:03:37] indra_db_rest.query_processor - Retrieving statements that have an agent where NAME=LEF1 with role=SUBJECT.\n", - "INFO: [2024-08-09 16:03:37] indra_db_rest.request_logs - Running 0th request for statements\n", - "INFO: [2024-08-09 16:03:37] indra_db_rest.request_logs - LIMIT: None\n", - "INFO: [2024-08-09 16:03:37] indra_db_rest.request_logs - OFFSET: 0\n", - "INFO: [2024-08-09 16:03:46] indra_db_rest.request_logs - Running 1st request for statements\n", - "INFO: [2024-08-09 16:03:46] indra_db_rest.request_logs - LIMIT: None\n", - "INFO: [2024-08-09 16:03:46] indra_db_rest.request_logs - OFFSET: 500\n", - "INFO: [2024-08-09 16:03:49] indra_db_rest.request_logs - Running 2nd request for statements\n", - "INFO: [2024-08-09 16:03:49] indra_db_rest.request_logs - LIMIT: None\n", - "INFO: [2024-08-09 16:03:49] indra_db_rest.request_logs - OFFSET: 1000\n", - "INFO: [2024-08-09 16:03:52] indra_db_rest.request_logs - Running 3rd request for statements\n", - "INFO: [2024-08-09 16:03:52] indra_db_rest.request_logs - LIMIT: None\n", - "INFO: [2024-08-09 16:03:52] indra_db_rest.request_logs - OFFSET: 1500\n", - "INFO: [2024-08-09 16:03:53] indra_db_rest.request_logs - Running 4th request for statements\n", - "INFO: [2024-08-09 16:03:53] indra_db_rest.request_logs - LIMIT: None\n", - "INFO: [2024-08-09 16:03:53] indra_db_rest.request_logs - OFFSET: 2000\n", - "INFO: [2024-08-09 16:03:56] indra_db_rest.request_logs - Running 5th request for statements\n", - "INFO: [2024-08-09 16:03:56] indra_db_rest.request_logs - LIMIT: None\n", - "INFO: [2024-08-09 16:03:56] indra_db_rest.request_logs - OFFSET: 2500\n", - "INFO: [2024-08-09 16:03:58] indra_db_rest.request_logs - Running 6th request for statements\n", - "INFO: [2024-08-09 16:03:58] indra_db_rest.request_logs - LIMIT: None\n", - "INFO: [2024-08-09 16:03:58] indra_db_rest.request_logs - OFFSET: 3000\n", - "INFO: [2024-08-09 16:04:00] indra_db_rest.request_logs - Running 7th request for statements\n", - "INFO: [2024-08-09 16:04:00] indra_db_rest.request_logs - LIMIT: None\n", - "INFO: [2024-08-09 16:04:00] indra_db_rest.request_logs - OFFSET: 3500\n", - "INFO: [2024-08-09 16:04:02] indra_db_rest.request_logs - Running 8th request for statements\n", - "INFO: [2024-08-09 16:04:02] indra_db_rest.request_logs - LIMIT: None\n", - "INFO: [2024-08-09 16:04:02] indra_db_rest.request_logs - OFFSET: 4000\n", - "INFO: [2024-08-09 16:04:04] indra_db_rest.request_logs - Running 9th request for statements\n", - "INFO: [2024-08-09 16:04:04] indra_db_rest.request_logs - LIMIT: None\n", - "INFO: [2024-08-09 16:04:04] indra_db_rest.request_logs - OFFSET: 4500\n", - "INFO: [2024-08-09 16:04:06] indra_db_rest.request_logs - Running 10th request for statements\n", - "INFO: [2024-08-09 16:04:06] indra_db_rest.request_logs - LIMIT: None\n", - "INFO: [2024-08-09 16:04:06] indra_db_rest.request_logs - OFFSET: 5000\n" - ] - } - ], - "source": [ - "ip = indra_db_rest.get_statements(subject='LEF1')" - ] - }, - { - "cell_type": "code", - "execution_count": 6, - "id": "9b9f7895", - "metadata": {}, - "outputs": [ - { - "name": "stderr", - "output_type": "stream", - "text": [ - "INFO: [2024-08-09 16:04:07] indra.tools.assemble_corpus - Filtering 5026 statements for ones containing \"all\" of: VSNL1, LRP4, EPHA7, TTC9, GLCE, CEMIP2, ADAMTSL2, PDZD8, AMOT, NOTUM, DKK4, CXCL14, GPCPD1, FABP4, VWA2, FNDC3A, CTNNA2, APCDD1, CRYBB1, RCN2, LEF1, CALML3, PLA2G4A, ACSL5...\n", - "INFO: [2024-08-09 16:04:07] indra.tools.assemble_corpus - 25 statements after filter...\n" + "INFO: [2024-08-09 16:09:54] indra_db_rest.query_processor - Retrieving statements that have an agent where NAME=LEF1 with role=SUBJECT.\n", + "INFO: [2024-08-09 16:09:54] indra_db_rest.request_logs - Running 0th request for statements\n", + "INFO: [2024-08-09 16:09:54] indra_db_rest.request_logs - LIMIT: None\n", + "INFO: [2024-08-09 16:09:54] indra_db_rest.request_logs - OFFSET: 0\n", + "INFO: [2024-08-09 16:09:55] indra_db_rest.request_logs - Running 1st request for statements\n", + "INFO: [2024-08-09 16:09:55] indra_db_rest.request_logs - LIMIT: None\n", + "INFO: [2024-08-09 16:09:55] indra_db_rest.request_logs - OFFSET: 500\n", + "INFO: [2024-08-09 16:09:57] indra_db_rest.request_logs - Running 2nd request for statements\n", + "INFO: [2024-08-09 16:09:57] indra_db_rest.request_logs - LIMIT: None\n", + "INFO: [2024-08-09 16:09:57] indra_db_rest.request_logs - OFFSET: 1000\n", + "INFO: [2024-08-09 16:09:58] indra_db_rest.request_logs - Running 3rd request for statements\n", + "INFO: [2024-08-09 16:09:58] indra_db_rest.request_logs - LIMIT: None\n", + "INFO: [2024-08-09 16:09:58] indra_db_rest.request_logs - OFFSET: 1500\n", + "INFO: [2024-08-09 16:09:59] indra_db_rest.request_logs - Running 4th request for statements\n", + "INFO: [2024-08-09 16:09:59] indra_db_rest.request_logs - LIMIT: None\n", + "INFO: [2024-08-09 16:09:59] indra_db_rest.request_logs - OFFSET: 2000\n", + "INFO: [2024-08-09 16:10:00] indra_db_rest.request_logs - Running 5th request for statements\n", + "INFO: [2024-08-09 16:10:00] indra_db_rest.request_logs - LIMIT: None\n", + "INFO: [2024-08-09 16:10:00] indra_db_rest.request_logs - OFFSET: 2500\n", + "INFO: [2024-08-09 16:10:01] indra_db_rest.request_logs - Running 6th request for statements\n", + "INFO: [2024-08-09 16:10:01] indra_db_rest.request_logs - LIMIT: None\n", + "INFO: [2024-08-09 16:10:01] indra_db_rest.request_logs - OFFSET: 3000\n", + "INFO: [2024-08-09 16:10:02] indra_db_rest.request_logs - Running 7th request for statements\n", + "INFO: [2024-08-09 16:10:02] indra_db_rest.request_logs - LIMIT: None\n", + "INFO: [2024-08-09 16:10:02] indra_db_rest.request_logs - OFFSET: 3500\n", + "INFO: [2024-08-09 16:10:03] indra_db_rest.request_logs - Running 8th request for statements\n", + "INFO: [2024-08-09 16:10:03] indra_db_rest.request_logs - LIMIT: None\n", + "INFO: [2024-08-09 16:10:03] indra_db_rest.request_logs - OFFSET: 4000\n", + "INFO: [2024-08-09 16:10:04] indra_db_rest.request_logs - Running 9th request for statements\n", + "INFO: [2024-08-09 16:10:04] indra_db_rest.request_logs - LIMIT: None\n", + "INFO: [2024-08-09 16:10:04] indra_db_rest.request_logs - OFFSET: 4500\n", + "INFO: [2024-08-09 16:10:04] indra_db_rest.request_logs - Running 10th request for statements\n", + "INFO: [2024-08-09 16:10:04] indra_db_rest.request_logs - LIMIT: None\n", + "INFO: [2024-08-09 16:10:04] indra_db_rest.request_logs - OFFSET: 5000\n", + "INFO: [2024-08-09 16:10:05] indra.tools.assemble_corpus - Filtering 5026 statements for ones containing \"all\" of: ACSL5, NOTUM, CRYBB1, DKK4, CALML3, CEMIP2, LRP4, LEF1, CXCL14, FNDC3A, RCN2, APCDD1, GLCE, PDZD8, VWA2, GPCPD1, ADAMTSL2, FABP4, AMOT, EPHA7, CTNNA2, PLA2G4A, TTC9, VSNL1...\n", + "INFO: [2024-08-09 16:10:05] indra.tools.assemble_corpus - 25 statements after filter...\n" ] } ], "source": [ - "from indra.tools import assemble_corpus as ac\n", - "stmts = ac.filter_gene_list(ip.statements, set(target_protein_names) - {'CTNNB1'} | {'LEF1'}, policy='all')" - ] - }, - { - "cell_type": "code", - "execution_count": 7, - "id": "7ed7a1bf", - "metadata": {}, - "outputs": [ - { - "data": { - "text/plain": [ - "[Activation(LEF1(), LEF1()),\n", - " DecreaseAmount(LEF1(), LEF1()),\n", - " Inhibition(LEF1(), LEF1()),\n", - " IncreaseAmount(LEF1(), LEF1()),\n", - " IncreaseAmount(LEF1(), LEF1()),\n", - " IncreaseAmount(LEF1(mods: (modification)), LEF1()),\n", - " DecreaseAmount(LEF1(), ACSL5()),\n", - " DecreaseAmount(LEF1(), VWA2()),\n", - " Complex(LEF1(), LEF1()),\n", - " Inhibition(LEF1(), LEF1()),\n", - " DecreaseAmount(LEF1(), PLA2G4A()),\n", - " DecreaseAmount(LEF1(), CTNNA2()),\n", - " DecreaseAmount(LEF1(), LEF1()),\n", - " DecreaseAmount(LEF1(), VSNL1()),\n", - " DecreaseAmount(LEF1(), FABP4()),\n", - " DecreaseAmount(LEF1(), LEF1(muts: (K, 86, E))),\n", - " DecreaseAmount(LEF1(mods: (modification)), LEF1()),\n", - " Phosphorylation(LEF1(), LEF1(mods: (phosphorylation))),\n", - " Activation(LEF1(), LEF1(muts: (None, None, None))),\n", - " DecreaseAmount(LEF1(), RCN2()),\n", - " DecreaseAmount(LEF1(), CEMIP2()),\n", - " Activation(LEF1(), LEF1()),\n", - " IncreaseAmount(LEF1(), LEF1(muts: (K, 86, E))),\n", - " DecreaseAmount(LEF1(), EPHA7()),\n", - " IncreaseAmount(LEF1(), DKK4())]" - ] - }, - "execution_count": 7, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "stmts" - ] - }, - { - "cell_type": "code", - "execution_count": 8, - "id": "a34c26fb", - "metadata": {}, - "outputs": [], - "source": [ - "stmts = [s for s in stmts if len({x.name for x in s.real_agent_list()}) > 1]" - ] - }, - { - "cell_type": "code", - "execution_count": 9, - "id": "6f8cf643", - "metadata": {}, - "outputs": [ - { - "data": { - "text/plain": [ - "[DecreaseAmount(LEF1(), ACSL5()),\n", - " DecreaseAmount(LEF1(), VWA2()),\n", - " DecreaseAmount(LEF1(), PLA2G4A()),\n", - " DecreaseAmount(LEF1(), CTNNA2()),\n", - " DecreaseAmount(LEF1(), VSNL1()),\n", - " DecreaseAmount(LEF1(), FABP4()),\n", - " DecreaseAmount(LEF1(), RCN2()),\n", - " DecreaseAmount(LEF1(), CEMIP2()),\n", - " DecreaseAmount(LEF1(), EPHA7()),\n", - " IncreaseAmount(LEF1(), DKK4())]" - ] - }, - "execution_count": 9, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "stmts" - ] - }, - { - "cell_type": "code", - "execution_count": 10, - "id": "71987146", - "metadata": {}, - "outputs": [], - "source": [ - "from indra.assemblers.html import HtmlAssembler" - ] - }, - { - "cell_type": "code", - "execution_count": 11, - "id": "fb01661b", - "metadata": {}, - "outputs": [], - "source": [ - "ha = HtmlAssembler(stmts)" - ] - }, - { - "cell_type": "code", - "execution_count": 12, - "id": "08bf5a71", - "metadata": {}, - "outputs": [], - "source": [ + "ip = indra_db_rest.get_statements(subject='LEF1')\n", + "stmts = ac.filter_gene_list(ip.statements, set(target_protein_names) - {'CTNNB1'} | {'LEF1'}, policy='all')\n", + "stmts = [s for s in stmts if len({x.name for x in s.real_agent_list()}) > 1]\n", + "ha = HtmlAssembler(stmts)\n", "_ = ha.make_model(grouping_level='statement')\n", - "ha.save_model('LEF1_explanations.html')" + "ha.save_model(os.path.join(output_folder, 'LEF1_explanations.html'))" ] }, { "cell_type": "code", - "execution_count": 13, + "execution_count": null, "id": "edc8b6d0", "metadata": {}, "outputs": [ @@ -397,53 +266,23 @@ "name": "stderr", "output_type": "stream", "text": [ - "INFO: [2024-08-09 16:04:07] indra_db_rest.query_processor - Retrieving statements that have an agent where NAME=TCF7L2 with role=SUBJECT.\n", - "INFO: [2024-08-09 16:04:07] indra_db_rest.request_logs - Running 0th request for statements\n", - "INFO: [2024-08-09 16:04:07] indra_db_rest.request_logs - LIMIT: None\n", - "INFO: [2024-08-09 16:04:07] indra_db_rest.request_logs - OFFSET: 0\n", - "INFO: [2024-08-09 16:04:12] indra_db_rest.request_logs - Running 1st request for statements\n", - "INFO: [2024-08-09 16:04:12] indra_db_rest.request_logs - LIMIT: None\n", - "INFO: [2024-08-09 16:04:12] indra_db_rest.request_logs - OFFSET: 500\n", - "INFO: [2024-08-09 16:04:14] indra_db_rest.request_logs - Running 2nd request for statements\n", - "INFO: [2024-08-09 16:04:14] indra_db_rest.request_logs - LIMIT: None\n", - "INFO: [2024-08-09 16:04:14] indra_db_rest.request_logs - OFFSET: 1000\n" - ] - } - ], - "source": [ - "ip = indra_db_rest.get_statements(subject='TCF7L2')" - ] - }, - { - "cell_type": "code", - "execution_count": 14, - "id": "597b4f6f", - "metadata": {}, - "outputs": [ - { - "name": "stderr", - "output_type": "stream", - "text": [ - "INFO: [2024-08-09 16:04:16] indra.tools.assemble_corpus - Filtering 1170 statements for ones containing \"all\" of: VSNL1, LRP4, EPHA7, TTC9, GLCE, CEMIP2, ADAMTSL2, PDZD8, TCF7L2, AMOT, NOTUM, DKK4, CXCL14, GPCPD1, FABP4, VWA2, FNDC3A, CTNNA2, APCDD1, CRYBB1, RCN2, LEF1, CALML3, PLA2G4A, ACSL5...\n", - "INFO: [2024-08-09 16:04:16] indra.tools.assemble_corpus - 11 statements after filter...\n" + "INFO: [2024-08-09 16:10:06] indra_db_rest.query_processor - Retrieving statements that have an agent where NAME=TCF7L2 with role=SUBJECT.\n", + "INFO: [2024-08-09 16:10:06] indra_db_rest.request_logs - Running 0th request for statements\n", + "INFO: [2024-08-09 16:10:06] indra_db_rest.request_logs - LIMIT: None\n", + "INFO: [2024-08-09 16:10:06] indra_db_rest.request_logs - OFFSET: 0\n", + "INFO: [2024-08-09 16:10:07] indra_db_rest.request_logs - Running 1st request for statements\n", + "INFO: [2024-08-09 16:10:07] indra_db_rest.request_logs - LIMIT: None\n", + "INFO: [2024-08-09 16:10:07] indra_db_rest.request_logs - OFFSET: 500\n" ] } ], "source": [ + "ip = indra_db_rest.get_statements(subject='TCF7L2')\n", "stmts = ac.filter_gene_list(ip.statements, set(target_protein_names) - {'CTNNB1'} | {'TCF7L2'}, policy='all')\n", - "stmts = [s for s in stmts if len({x.name for x in s.real_agent_list()}) > 1]" - ] - }, - { - "cell_type": "code", - "execution_count": 15, - "id": "7e28bd00", - "metadata": {}, - "outputs": [], - "source": [ + "stmts = [s for s in stmts if len({x.name for x in s.real_agent_list()}) > 1]\n", "ha = HtmlAssembler(stmts)\n", "_ = ha.make_model(grouping_level='statement')\n", - "ha.save_model('TCF7L2_explanations.html')" + "ha.save_model(os.path.join(output_folder, 'TCF7L2_explanations.html'))" ] } ],