Transcription regulation by murine B-myb is distinct from that by c-myb.
The transcription regulatory properties of murine B-myb protein were compared to those of c-myb. Whereas c-Myb trans-activated an SV40 early promoter containing multiple copies of an upstream c-Myb DNA-binding site (MBS-1), and similarly the human c-myc promoter, B-Myb was unable to do so. Full-length B-Myb translated in vitro did not bind MBS-1; however, truncation of the B-Myb C-terminus or fusion of the B-Myb DNA-binding domain to the c-Myb C-terminus showed that it was inherently competent to interact with this motif. Further evidence from co-transfection experiments, demonstrating that B-Myb inhibited trans-activation by c-Myb, suggested that failure of B-Myb to trans-activate these promoters did not simply occur through lack of binding to MBS-1. Moreover, using GAL4/B-Myb fusions, it was found that an acidic region of B-Myb, which by comparison to c-Myb was expected to contain a transcription activation domain, actually had no inherent trans-activation activity and indeed appeared to trans-inhibit c-Myb. In contrast to the above findings, both B-Myb and c-Myb were able to weakly trans-activate the DNA polymerase alpha promoter. Results obtained here demonstrate that the activities of B-Myb and c-Myb are clearly distinct and suggest that these related proteins may have different functions in regulation of target gene expression.
Ludwig Institute for Cancer Research, St Mary's Hospital Medical School, London, UK.
R J
RJ
Watson
C
C
Robinson
E W
EW
Lam
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D004247:DNA; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D016259:Genes, myc; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020598:Proto-Oncogene Proteins c-myb; D029701:Saccharomyces cerevisiae Proteins; D013539:Simian virus 40 / Q000235:genetics; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; C064352:MYBL2 protein, human; C499306:Mybl2 protein, mouse; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D004247:DNA