HMG box transcription factor TCF-4's interaction with CtBP1 controls the expression of the Wnt target Axin2/ Conductin in human embryonic kidney cells.
Members of the Tcf/Lef family of the HMG box transcription factors are nuclear effectors of the Wnt signal transduction pathway. Upon Wnt signaling, TCF/LEF proteins interact with beta-catenin and activate transcription of target genes, while, in the absence of the Wnt signal, TCFs function as transcriptional repressors. All vertebrate Tcf/Lef transcription factors associate with TLE/Groucho-related co-repressors, and here we provide evidence for an interaction between the C-terminus of the TCF-4 HMG box protein and the C-terminal binding protein 1 ( CtBP1) transcriptional co-repressor. Using Wnt-1-stimulated human embryonic kidney 293 cells, we show that CtBP1 represses the transcriptional activity of a Tcf/ beta-catenin-dependent synthetic promoter and, furthermore, decreases the expression of the endogenous Wnt target, Axin2/ Conductin. The CtBP1-mediated repression was alleviated by trichostatin A treatment, indicating that the CtBP inhibitory mechanism is dependent on the activity of histone deacetylases.[1]References
- HMG box transcription factor TCF-4's interaction with CtBP1 controls the expression of the Wnt target Axin2/Conductin in human embryonic kidney cells. Valenta, T., Lukas, J., Korinek, V. Nucleic Acids Res. (2003) [Pubmed]
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