Drosophila CBP represses the transcription factor TCF to antagonize Wingless signalling.
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.
MRC Laboratory of Molecular Biology, Cambridge, UK.
L
L
Waltzer
M
M
Bienz
D000818:Animals; D051186:Armadillo Domain Proteins; D050882:CREB-Binding Protein; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins; D006609:High Mobility Group Proteins / Q000378:metabolism; D019476:Insect Proteins / Q000235:genetics; D051821:Lymphoid Enhancer-Binding Factor 1; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013489:Suppression, Genetic; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014158:Transcription, Genetic; D051155:Wnt1 Protein
C495305:ARM protein, Drosophila; D051186:Armadillo Domain Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006609:High Mobility Group Proteins; D019476:Insect Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051155:Wnt1 Protein; C074622:wg protein, Drosophila; D050882:CREB-Binding Protein