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.
Valenta
Tomas
T
Institute of Molecular Genetics Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague 4, Czech Republic.
Lukas
Jan
J
Korinek
Vladimir
V
D000429:Alcohol Oxidoreductases; D000595:Amino Acid Sequence; D000818:Animals; D060466:Axin Protein; D019556:COS Cells; D002460:Cell Line; D056970:Co-Repressor Proteins; D018920:Coculture Techniques; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D051820:TCF Transcription Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin
C491761:AXIN2 protein, human; D060466:Axin Protein; C111729:Axin2 protein, mouse; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D056970:Co-Repressor Proteins; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D006877:Hydroxamic Acids; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; C544895:Tcf7l2 protein, mouse; C553059:Tcf7l2 protein, rat; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; C495247:WNT1 protein, human; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; C495245:Wnt1 protein, rat; D029961:Zebrafish Proteins; D051176:beta Catenin; C012589:trichostatin A; D000429:Alcohol Oxidoreductases; C111341:Ctbp2 protein, mouse; C096794:C-terminal binding protein