B-Myb: A Key Regulator of the Cell Cycle

Publisher Summary The chapter describes that B-Myb gene is subjected to two putative cyclin-dependent regulatory mechanisms during the cell cycle that is upregulation of mRNA abundance by derepression of E2F/DRS-regulated transcription at the G1/S boundary, and phosphorylation of the protein during S phase. This dual mechanism has several features. First, it ensures that in quiescent cells, there is effectively no active B-Myb because transcription is greatly down regulated and the little protein that may be produced is not activated by cyclin-dependent kinases (Cdk)-mediated phosphorylation. Second, it allows for a huge increase in active B-Myb as cells go from the G1 phase into S phase. Third, in cycling cells, the B-Myb produced in S phase may be partially inactivated by dephosphorylation at later stages and only hyperactivated again on entry into the subsequent S phase. The precise role of B-myb in cell cycle regulation is still unknown. B-Myb as a transcriptional activator is foreseen to have function in regulation of other genes whose products are involved in synthesis of the components of nucleotide biosynthesis and DNA replication. As a transcriptional repressor, B-Myb is considered in extinguishing expression of negative regulators of cell proliferation. BMyb has the potential to activate transcription from promoters that lack Myb binding site (MBS), and these genes cannot be predicted from database searches. The realization that B-Myb is subject to controls on both its abundance and activity, that this directs maximal activity to S phase, and that B-Myb function appears to be necessary for cell proliferation leads to conclude that it plays a central role downstream of the cyclins in controlling the basic mechanisms that coordinate passage through the cell cycle.