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.
Bessa
M
M
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.
Joaquin
M
M
Tavner
F
F
Saville
M K
MK
Watson
R J
RJ
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