Drosophila CBP represses the transcription factor TCF to antagonize Wingless signalling

Nature. 1998 Oct 1;395(6701):521-5. doi: 10.1038/26785.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Armadillo Domain Proteins
  • CREB-Binding Protein
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / metabolism*
  • Drosophila
  • Drosophila Proteins*
  • High Mobility Group Proteins / metabolism
  • Insect Proteins / genetics
  • Lymphoid Enhancer-Binding Factor 1
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / metabolism*
  • Suppression, Genetic
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Wnt1 Protein

Substances

  • ARM protein, Drosophila
  • Armadillo Domain Proteins
  • DNA-Binding Proteins
  • Drosophila Proteins
  • High Mobility Group Proteins
  • Insect Proteins
  • Lymphoid Enhancer-Binding Factor 1
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Trans-Activators
  • Transcription Factors
  • Wnt1 Protein
  • wg protein, Drosophila
  • CREB-Binding Protein