Cubitus interruptus requires Drosophila CREB-binding protein to activate wingless expression in the Drosophila embryo

CREB-binding protein (CBP) serves as a transcriptional coactivator in multi ple signal transduction pathways. The Drosophila homologue of CBP, dCBP, in teracts with the transcription factors Cubitus interruptus (CI), MAD, and D orsal (DL) and functions as a coactivator in several signaling pathways dur ing Drosophila development, including the hedgehog (hh), decapentaplegic (d pp), and Toll pathways. Although dCBP is required for the expression of the hh target genes, wingless (wg) and patched (ptc) in vivo, and potentiates ci-mediated transcriptional activation in vitro, it is not known that ci ab solutely requires dCBP for its activity. We used a yeast genetic screen to identify several ci point mutations that disrupt CI-dCBP interactions. Thes e mutant proteins are unable to transactivate a reporter gene regulated by ci binding sites and have a lower dCBP-stimulated activity than wild-type C I. When expressed exogenously in embryos, the CI point mutants cannot activ ate endogenous wg expression. Furthermore, a CI mutant protein that lacks t he entire dCBP interaction domain functions as a negative competitor for wi ld-type CI activity, and the expression of dCBP antisense RNAs can suppress Ct transactivation in Kc cells. Taken together, our data suggest that dCBP function is necessary for ci-mediated transactivation of wg during Drosoph ila embryogenesis.