TLE oligomerizes

Stable Identifier
Reaction [transition]
Homo sapiens
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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, Waterman, ML, Pate, KT

BMC Cancer 2009
15121853 Groucho oligomerization is required for repression in vivo

Hasson, P, Paroush, Z, Song, H, Courey, AJ

Mol. Cell. Biol. 2004
15768032 Beta-catenin directly displaces Groucho/TLE repressors from Tcf/Lef in Wnt-mediated transcription activation

Weis, WI, Daniels, DL

Nat Struct Mol Biol 2005
9751710 Transcriptional repression by AML1 and LEF-1 is mediated by the TLE/Groucho corepressors

Paroush, Z, Goldstein, RE, Groner, Y, Tang, H, Bernstein, Y, Levanon, D, Goldenberg, D, Stifani, S

Proc. Natl. Acad. Sci. U.S.A. 1998
11266540 All Tcf HMG box transcription factors interact with Groucho-related co-repressors

van De Wetering, M, Clevers, HC, Brantjes, H, Roose, J

Nucleic Acids Res. 2001
9819412 A role for Groucho tetramerization in transcriptional repression

Chen, G, Courey, AJ, Nguyen, PH

Mol. Cell. Biol. 1998
11934263 TCF: Lady Justice casting the final verdict on the outcome of Wnt signalling

Barker, N, Clevers, HC, Brantjes, H, van Es, J

Biol. Chem. 2002
10485845 A functional interaction between the histone deacetylase Rpd3 and the corepressor groucho in Drosophila development

Chen, G, Mische, S, Fernandez, J, 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
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