Repression of WNT target genes

Stable Identifier
R-HSA-4641265
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Pathway
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Homo sapiens
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In the absence of a WNT signal, many WNT target genes are repressed by Groucho/TLE. Groucho was initially identified in Drosophila, where it has been shown to interact with a variety of proteins to repress transcription (reviewed in Turki-Judeh and Courey, 2012). Groucho proteins, including the 4 human homologues (transducin-like enhancer of split (TLE) 1-4), do not bind DNA directly but instead are recruited to target genes through interaction with DNA-binding transcription factors including TCF/LEF (Brantjes et al, 2001; reviewed in Chen and Courey, 2000). Groucho proteins are believed to oligomerize in a manner that depends on an N-terminal glutamine-rich Q domain, and oligomerization may be important for function (Song et al, 2004; Pinto and Lobe, 1996). Groucho/TLE proteins affect levels of gene expression by interacting with the core transcriptional machinery as well as by modfiying chromatin structure through direct interaction with histones and recruitment of histone deacetylases, among other mechanisms (reviewed in Turki-Judeh and Courey, 2012). In addition to the four TLE proteins, human cells also include a truncated TLE-like protein called amino-terminal enhancer of split (AES) which contains the N-terminal Q domain but lacks much of the C-terminal sequence of TLE proteins, including the WD domain which is important for many protein-protein interactions. AES is believed to act as a dominant negative, since it is able to heter-oligomerize with full-length TLE proteins to form non-functional complexes (Brantjes et al, 2001; reviewed in Beagle and Johnson, 2010).

Literature References
PubMed ID Title Journal Year
20925119 AES/GRG5: more than just a dominant-negative TLE/GRG family member

Beagle, B, Johnson, GV

Dev. Dyn. 2010
15121853 Groucho oligomerization is required for repression in vivo

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

Mol. Cell. Biol. 2004
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
22305159 Groucho: a corepressor with instructive roles in development

Turki-Judeh, W, Courey, AJ

Curr. Top. Dev. Biol. 2012
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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