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.
Mesh Terms:
Alcohol Oxidoreductases, Amino Acid Sequence, Animals, COS Cells, Cell Line, Coculture Techniques, Cytoskeletal Proteins, DNA-Binding Proteins, Gene Expression Regulation, Humans, Hydroxamic Acids, Mice, Molecular Sequence Data, Phosphoproteins, Plasmids, Protein Binding, Proto-Oncogene Proteins, RNA, Messenger, Rats, Repressor Proteins, Sequence Homology, Amino Acid, TCF Transcription Factors, Trans-Activators, Transcription Factor 7-Like 2 Protein, Transcription Factors, Transcription, Genetic, Transfection, Wnt Proteins, Wnt1 Protein, Zebrafish Proteins, beta Catenin
Nucleic Acids Res.
Date: May. 01, 2003
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