Reactome | Deactivation of the beta-catenin transactivating complex

Deactivation of the beta-catenin transactivating complex

Stable Identifier

R-HSA-3769402

DOI

10.3180/r-hsa-3769402.1

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

Deactivation of the beta-catenin transactivating complex

Click the image above or here to open this pathway in the Pathway Browser

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 (Bauer et al, 2000; Weiske et al, 2007; Song and Gelmann, 2008). 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 (Takemaru et al, 2003; Li et al, 2008; Tago et al, 2000; Graham et al, 2002; Daniels and Weiss, 2002). Chibby additionally promotes the nuclear export of beta-catenin in conjunction with 14-3-3/YWHAZ proteins (Takemura et al, 2003; Li et al, 2008). A couple of recent studies have also suggested a role for nuclear APC in the disassembly of the beta-catenin activation complex (Hamada and Bienz, 2004; Sierra et al, 2006). 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).

Literature References

PubMed ID	Title	Journal	Year
12408825	ICAT inhibits beta-catenin binding to Tcf/Lef-family transcription factors and the general coactivator p300 using independent structural modules Daniels, DL, Weis, WI	Mol. Cell	2002
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
18632669	Silencing mediator for retinoid and thyroid hormone receptor and nuclear receptor corepressor attenuate transcriptional activation by the beta-catenin-TCF4 complex Song, LN, Gelmann, EP	J. Biol. Chem.	2008
10898789	Inhibition of Wnt signaling by ICAT, a novel beta-catenin-interacting protein Tago, K, Nakamura, T, Nishita, M, Hyodo, J, Nagai, S, Murata, Y, Adachi, S, Ohwada, S, Morishita, Y, Shibuya, H, Akiyama, T	Genes Dev.	2000
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
18573912	Chibby cooperates with 14-3-3 to regulate beta-catenin subcellular distribution and signaling activity Li, FQ, Mofunanya, A, Harris, K, Takemaru, K	J. Cell Biol.	2008
11080158	Pontin52 and reptin52 function as antagonistic regulators of beta-catenin signalling activity Bauer, A, Chauvet, S, Huber, O, Usseglio, F, Rothbächer, U, Aragnol, D, Kemler, R, Pradel, J	EMBO J.	2000
19364920	Inactivation of Chibby affects function of motile airway cilia Voronina, VA, Takemaru, K, Treuting, PM, Love, D, Grubb, BR, Hajjar, AM, Adams, A, Li, FQ, Moon, RT	J. Cell Biol.	2009
12408824	The crystal structure of the beta-catenin/ICAT complex reveals the inhibitory mechanism of ICAT Graham, TA, Clements, WK, Kimelman, D, Xu, W	Mol. Cell	2002
18077326	The tumor suppressor Fhit acts as a repressor of beta-catenin transcriptional activity Weiske, J, Albring, KF, Huber, O	Proc. Natl. Acad. Sci. U.S.A.	2007
12712206	Chibby, a nuclear beta-catenin-associated antagonist of the Wnt/Wingless pathway Takemaru, K, Yamaguchi, S, Lee, YS, Zhang, Y, Carthew, RW, Moon, RT	Nature	2003