Deactivation of the beta-catenin transactivating complex

Stable Identifier
R-HSA-3769402
Type
Pathway
Species
Homo sapiens
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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
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
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
19364920 Inactivation of Chibby affects function of motile airway cilia

Voronina, VA, Takemaru, K, Treuting, P, Love, D, Grubb, BR, Hajjar, AM, Adams, A, Li, FQ, Moon, RT

J. Cell Biol. 2009
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
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
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
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
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
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
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
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