Reactome | TLE oligomerizes

TLE oligomerizes

Stable Identifier

R-HSA-4641229

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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TCF1, LEF1, TCF3 and TCF4 are HMG box-containing DNA-binding proteins that recognize WNT-responsive elements (WREs) in the promoters of WNT target genes (reviewed in Brantjes et al, 2002). In the absence of a WNT signal, promoter-bound TCF/LEF is bound by one of four Groucho homologues, TLE1, 2, 3 or 4 (Levanon et al, 1998; Brantjes et al, 2001; Daniels and Weis, 2005). Groucho/TLE proteins are co-repressors for a variety of DNA-binding transcription factors and mediate repression at least in part through their interaction with histone deacetylases such as RPD3/HDAC1 (Arce et al, 2009; Brantjes et al, 2001; Chen et al, 1999; reviewed in Chen and Courey, 2000). Groucho proteins have been shown to homo-tetramerize through a glutamine rich Q domain at the N-terminus, and this oligomerization is required for repression. The Q domain is also sufficient for interaction with TCF/LEF proteins (Brantjes et al, 2001; Chen et al, 1998; Pinto and Lobe, 1996; Song et al, 2004). Studies with purified proteins have shown that human TLE1 and 2 bind to an amino-terminal truncated form of LEF1(69-397) with an affinity comparable to that for full length LEF1 (Daniels and Weis, 2005).

Literature References

PubMed ID	Title	Journal	Year
19460168	Groucho binds two conserved regions of LEF-1 for HDAC-dependent repression Arce, L, Pate, KT, Waterman, ML	BMC Cancer	2009
15121853	Groucho oligomerization is required for repression in vivo Song, H, Hasson, P, Paroush, Z, Courey, AJ	Mol. Cell. Biol.	2004
15768032	Beta-catenin directly displaces Groucho/TLE repressors from Tcf/Lef in Wnt-mediated transcription activation Daniels, DL, Weis, WI	Nat Struct Mol Biol	2005
9751710	Transcriptional repression by AML1 and LEF-1 is mediated by the TLE/Groucho corepressors Levanon, D, Goldstein, RE, Bernstein, Y, Tang, H, Goldenberg, D, Stifani, S, Paroush, Z, Groner, Y	Proc. Natl. Acad. Sci. U.S.A.	1998
11266540	All Tcf HMG box transcription factors interact with Groucho-related co-repressors Brantjes, H, Roose, J, van De Wetering, M, Clevers, HC	Nucleic Acids Res.	2001
9819412	A role for Groucho tetramerization in transcriptional repression Chen, G, Nguyen, PH, Courey, AJ	Mol. Cell. Biol.	1998
11934263	TCF: Lady Justice casting the final verdict on the outcome of Wnt signalling Brantjes, H, Barker, N, van Es, J, Clevers, HC	Biol. Chem.	2002
10485845	A functional interaction between the histone deacetylase Rpd3 and the corepressor groucho in Drosophila development Chen, G, Fernandez, J, Mische, S, Courey, AJ	Genes Dev.	1999
8955148	Products of the grg (Groucho-related gene) family can dimerize through the amino-terminal Q domain Pinto, M, Lobe, CG	J. Biol. Chem.	1996
10831834	Groucho/TLE family proteins and transcriptional repression Chen, G, Courey, AJ	Gene	2000