Deactivation of the beta-catenin transactivating complex

The mechanisms involved in downregulation of TCF-dependent transcription are not yet very well understood. beta-catenin is known to recruit a number of transcriptional repressors, including Reptin, SMRT and NCoR, to the TCF/LEF complex, allowing the transition from activation to repression. CTNNBIP1 (also known as ICAT) and Chibby are inhibitors of TCF-dependent signaling that function by binding directly to beta-catenin and preventing interactions with critical components of the transactivation machinery. Chibby additionally promotes the nuclear export of beta-catenin in conjunction with 14-3-3/YWHAZ proteins. A couple of recent studies have also suggested a role for nuclear APC in the disassembly of the beta-catenin activation complex. It is worth noting that while some of the players involved in the disassembly of the beta-catenin transactivating complex are beginning to be worked out in vitro, the significance of their role in vivo is not yet fully understood, and some can be knocked out with little effect on endogenous WNT signaling (see for instance Voronina et al, 2009).

Summary from Reactome (R-HSA-3769402), read 2026-09-23.