B-Myb: A Highly Regulated Member Of The Myb Transcription Factor Family

Expression of the B-myb transcription factor gene is regulated at two major levels during the mammalian cell cycle. Transcriptional regulation by an E2Fdependent mechanism directs maximal expression levels of B-Myb protein to late G1/S, while phosphorylation of B-Myb by Cyclin A/Cdk2 at the G1/S transition and during S phase enhances its transactivation properties. B-myb is an essential gene for early embryonic development, and the timing of its regulation strongly suggests that its most critical functions are required during S phase. In addition to its presumptive role in regulating gene expression, recent evidence also suggests that B-Myb displays additional nontranscriptional activities, for example through its binding to the p107 retinoblastoma-related protein. This chapter reviews how B-Myb activity is regulated by hyperphophorylation during the cell cycle and addresses how this may contribute to cell growth control.