Journal Article

HMG box transcription factor TCF‐4’s interaction with CtBP1 controls the expression of the Wnt target Axin2/Conductin in human embryonic kidney cells

Tomas Valenta, Jan Lukas and Vladimir Korinek

in Nucleic Acids Research

Volume 31, issue 9, pages 2369-2380
Published in print May 2003 | ISSN: 0305-1048
Published online May 2003 | e-ISSN: 1362-4962 | DOI: https://dx.doi.org/10.1093/nar/gkg346
HMG box transcription factor TCF‐4’s interaction with CtBP1 controls the expression of the Wnt target Axin2/Conductin in human embryonic kidney cells

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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 β‐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/β‐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.

Journal Article.  10207 words.  Illustrated.

Subjects: Chemistry ; Biochemistry ; Bioinformatics and Computational Biology ; Genetics and Genomics ; Molecular and Cell Biology

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