TLE tetramers bind TCF/LEF at WNT promoters

Stable Identifier
R-HSA-8944349
Type
Reaction [binding]
Species
Homo sapiens
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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
15121853 Groucho oligomerization is required for repression in vivo

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

Mol. Cell. Biol. 2004
19460168 Groucho binds two conserved regions of LEF-1 for HDAC-dependent repression

Arce, L, Pate, KT, Waterman, ML

BMC Cancer 2009
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
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
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
9819412 A role for Groucho tetramerization in transcriptional repression

Chen, G, Nguyen, PH, Courey, AJ

Mol. Cell. Biol. 1998
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
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