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
PubMed ID Title Journal Year
16510874 The APC tumor suppressor counteracts beta-catenin activation and H3K4 methylation at Wnt target genes

Sierra, J, Yoshida, T, Joazeiro, CA, Jones, KA

Genes Dev. 2006
14600025 Crystal structure of a beta-catenin/axin complex suggests a mechanism for the beta-catenin destruction complex

Xing, Y, Clements, WK, Kimelman, D, Xu, W

Genes Dev. 2003
19928349 Nuclear APC

Neufeld, KL

Adv. Exp. Med. Biol. 2009
15327769 Crystal structure of a beta-catenin/APC complex reveals a critical role for APC phosphorylation in APC function

Xing, Y, Clements, WK, Le Trong, I, Hinds, TR, Stenkamp, R, Kimelman, D, Xu, W

Mol Cell 2004
15525529 The APC tumor suppressor binds to C-terminal binding protein to divert nuclear beta-catenin from TCF

Hamada, F, Bienz, M

Dev. Cell 2004
Participants
Participant Of
Orthologous Events
Authored
Reviewed