Drosophila melanogaster possesses a single gene, Dm myb, that is closely related to the vertebrate family of Myb genes, which encode transcription factors involved in regulatory decisions affecting cell proliferation, differentiation and apoptosis. In proliferating cells, the Dm myb gene product, DMyb, promotes both S-phase and M-phase, and acts to preserve diploidy by suppressing endoreduplication. The CBP and p300 proteins are transcriptional co-activators that interact with a multitude of transcription factors, including Myb. In transient transfection assays, transcriptional activation by DMyb is enhanced by co-expression of the Drosophila CBP protein, dCBP. Genetic interaction analysis reveals that these genes work together to promote mitosis, thereby demonstrating the physiological relevance of the biochemical interaction between the Myb and CBP proteins within a developing organism.