Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alcohol Oxidoreductases
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Amino Acid Sequence
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Animals
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Axin Protein
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COS Cells
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Cell Line
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Co-Repressor Proteins
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Coculture Techniques
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Cytoskeletal Proteins / genetics*
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Cytoskeletal Proteins / metabolism
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Gene Expression Regulation / drug effects
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Humans
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Hydroxamic Acids / pharmacology
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Mice
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Molecular Sequence Data
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Phosphoproteins / genetics
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Phosphoproteins / metabolism*
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Plasmids / genetics
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Protein Binding
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / physiology*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Sequence Homology, Amino Acid
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TCF Transcription Factors
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Transcription Factor 7-Like 2 Protein
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcription, Genetic
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Transfection
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Wnt Proteins
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Wnt1 Protein
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Zebrafish Proteins*
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beta Catenin
Substances
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AXIN2 protein, human
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Axin Protein
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Axin2 protein, mouse
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CTNNB1 protein, human
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CTNNB1 protein, mouse
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Co-Repressor Proteins
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Ctnnb1 protein, rat
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Cytoskeletal Proteins
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DNA-Binding Proteins
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Hydroxamic Acids
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Phosphoproteins
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Proto-Oncogene Proteins
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RNA, Messenger
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Repressor Proteins
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TCF Transcription Factors
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TCF7L2 protein, human
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Tcf7l2 protein, mouse
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Tcf7l2 protein, rat
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Trans-Activators
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Transcription Factor 7-Like 2 Protein
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Transcription Factors
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WNT1 protein, human
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Wnt Proteins
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Wnt1 Protein
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Wnt1 protein, mouse
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Wnt1 protein, rat
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Zebrafish Proteins
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beta Catenin
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trichostatin A
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Alcohol Oxidoreductases
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Ctbp2 protein, mouse
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C-terminal binding protein