ACTIVATION OF HUMAN B-MYB BY CYCLINS

B-MYB expression is associated with cell proliferation and recent stud ies have suggested that it promotes the S phase of mammalian cells. Ba sed on its homology to the transcription factors c-MYB and A-MYB, B-MY B is thought to be involved in transcriptional regulation; however, it s activity is not detectable in several cell lines. It was postulated that B-MYB function may depend on the presence of a cofactor, and rece nt studies suggested that B-MYB is phosphorylated specifically during S phase in murine fibroblasts. In this report we provide evidence that the product of the human B-myb gene can be activated in vivo by coexp ression with cyclin A or cyclin E. Transfection studies showed that B- MYB was a weak transcriptional activator in SAOS-2 cells and was unabl e to promote their proliferation. In contrast, overexpression of both B-MYB and cyclin A or cyclin E caused a drastic increase in the number of SAOS-2 cells in S phase. Also, overexpression of cyclin A and cycl in E in SAOS-2 cells enhanced the ability of B-MYB, but not c-MYB, to transactivate various promoters, including the cdc2 promoter, the HIV- 1-LTR, and the simian virus 40 minimal promoter. A direct role for cyc lin-dependent activation of B-MYB was demonstrated using an in vitro t ranscription assay. These observations suggest that one mechanism by w hich cyclin A and E may promote the S phase is through modification an d activation of B-MYB.