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Drosophila CBP represses the transcription factor TCF to antagonize Wingless signalling

Nature volume 395, pages 521–525 (1998)Cite this article

Abstract

T-cell factor (TCF), a high-mobility-group domain protein, is the transcription factor activated by Wnt/Wingless signalling1,2,3,4. When signalling occurs, TCF binds to its coactivator, beta-catenin/Armadillo, and stimulates the transcription of the target genes of Wnt/Wingless by binding to TCF-responsive enhancers1,5. Inappropriate activation of TCF in the colon epithelium and other cells leads to cancer6,7,8. It is therefore desirable for unstimulated cells to have a negative control mechanism to keep TCF inactive. Here we report that Drosophila CREB-binding protein (dCBP)9,10 binds to dTCF. dCBP mutants show mild Wingless overactivation phenotypes in various tissues. Consistent with this, dCBP loss-of-function suppresses the effects of armadillo mutation. Moreover, our data show that dCBP acetylates a conserved lysine in the Armadillo-binding domain of dTCF, and that this acetylation lowers the affinity of Armadillo binding to dTCF. Although CBP is a coactivator of other transcription factors11,12, our data show that CBP represses TCF.

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Figure 1: dCBP interacts with dTCF.
Figure 2: nej mutants mimic overactivation of the Wingless pathway.
Figure 3: Genetic interactions between nej and Wingless pathway mutants.
Figure 4: dCBP acetylates the Armadillo-binding domain of dTCF.

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Acknowledgements

We thank S. Ishii for nej mutants and plasmids; X. Yu, S. Greaves and J.-P. Vincent for strains and for sharing unpublished results; D. Owen for synthetic peptides; T. Kouzarides and R.Grosschedl for plasmids; M. Peifer and P. Simpson for fly strains; and X. Yu, M. Freeman and H. Pelham for discussion. L.W. is supported by an EMBO long-term fellowship.

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  1. MRC Laboratory of Molecular Biology, Hills Road, CB2 2QH, Cambridge, UK

    Lucas Waltzer & Mariann Bienz

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  1. Lucas Waltzer
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  2. Mariann Bienz
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Correspondence to Mariann Bienz.

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Waltzer, L., Bienz, M. Drosophila CBP represses the transcription factor TCF to antagonize Wingless signalling. Nature 395, 521–525 (1998). https://doi.org/10.1038/26785

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