Regulation of the cell cycle by B-Myb.
B-Myb is a cell-cycle-regulated member of the Myb transcription factor and, like c-Myb, has been implicated in regulation of hematopoietic cell proliferation and differentiation. In this study we have examined the mechanisms by which B-Myb regulates the cell cycle. We found that the ability of B-Myb both to promote Saos-2 cells into the S phase of the cell cycle and to overcome G1 arrest mediated by overexpression of the retinoblastoma-related p107 protein was correlated with the capacity of B-Myb to form an in vivo complex with p107, but was independent of its transactivation function. Further experiments using a B-Myb dominant-negative protein suggested that transcriptional activation of genes regulated through Myb DNA-binding sequences was required for cell proliferation. Our experiments suggest, therefore, that B-Myb influences cell cycle progression at two distinct levels: by inhibiting p107 and by inducing transcription of specific target genes.
Ludwig Institute for Cancer Research, Section of Virology and Cell Biology, Imperial College School of Medicine, St. Mary's Campus, Norfolk Place, London, W2 1PG, United Kingdom.
M
M
Bessa
M
M
Joaquin
F
F
Tavner
M K
MK
Saville
R J
RJ
Watson
D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D015534:Trans-Activators / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C064352:MYBL2 protein, human; D015534:Trans-Activators