Reactome: A Curated Pathway Database

APC promotes disassembly of beta-catenin transactivation complex

Stable Identifier
R-HSA-3364042
Type
Reaction [BlackBoxEvent]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

Studies in mouse myoblast and colorectal cancer cell lines show that APC, beta-TrCP and the CTBP corepressor are present at the MYC enhancer at times when beta-catenin and its associated coactivators are also present. Binding of APC is correlated with dissociation of the activator complex and precedes recruitment of TLE1 and HDAC1, suggesting that APC may promote the exchange between activator and repressor complexes at the enhancer (Sierra et al, 2006). CSNK1gamma phosphorylation of APC strongly increases its affinity for beta-catenin, and a phosphorylated APC fragment disrupts the formation of a DNA:LEF1:beta-catenin complex by EMSA, consistent with previous reports (Xing et al, 2003; Xing et al, 2004; Sierra et al, 2006). Because beta-catenin is unable to simultaneously bind APC and TCF/LEF, however, the mechanism of APC recruitment to the enhancer complex is unclear (Sierra et al, 2006). Full-length APC associates with CTBP in vitro and in vivo (Hamada and Bienz, 2004; Sierra et al, 2006) while Class I and Class II mutant APC proteins, which are commonly found in colorectal cancers, do not (Sierra et al, 2006; reviewed in Neufeld, 2009). CTBP repressor functions may therefore include facilitating the exchange of coactivator and corepressor complexes at WNT target genes.

Literature References
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