Drosophila CBP represses the transcription factor TCF to antagonize Wingless signalling.

Abstract:

:T-cell factor (TCF), a high-mobility-group domain protein, is the transcription factor activated by Wnt/Wingless signalling. 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 enhancers. Inappropriate activation of TCF in the colon epithelium and other cells leads to cancer. 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) 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 factors, our data show that CBP represses TCF.

journal_name

Nature

journal_title

Nature

authors

Waltzer L,Bienz M

doi

10.1038/26785

subject

Has Abstract

pub_date

1998-10-01 00:00:00

pages

521-5

issue

6701

eissn

0028-0836

issn

1476-4687

journal_volume

395

pub_type

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