The C-terminal domain of B-Myb acts as a positive regulator of transcription and modulates its biological functions.
The myb gene family consists of three members, named A-, B-, and c-myb. All three members of this family encode nuclear proteins that bind DNA in a sequence-specific manner and function as regulators of transcription. In this report, we have examined the biochemical and biological activities of murine B-myb and compared these properties with those of murine c-myb. In transient transactivation assays, murine B-myb exhibited transactivation potential comparable to that of c-myb. An analysis of deletion mutants of B-myb and c-myb showed that while the C-terminal domain of c-Myb acts as a negative regulator of transcriptional transactivation, the C-terminal domain of B-Myb functions as a positive enhancer of transactivation. To compare the biological activities of c-myb and B-myb, the two genes were overexpressed in 32Dcl3 cells, which are known to undergo terminal differentiation into granulocytes in the presence of granulocyte colony-stimulating factor (G-CSF). We observed that c-myb blocked the G-CSF-induced terminal differentiation of 32Dcl3 cells, resulting in their continued proliferation in the presence of G-CSF. In contrast, ectopic overexpression of B-myb blocked the ability of 32D cells to proliferate in the presence of G-CSF and accelerated the G-CSF-induced granulocytic differentiation of these cells. Similar studies with B-myb-c-myb chimeras showed that only chimeras that contained the C-terminal domain of B-Myb were able to accelerate the G-CSF-induced terminal differentiation of 32Dcl3 cells. These studies show that c-myb and B-myb do not exhibit identical biological activities and that the carboxyl-terminal regulatory domain of B-Myb plays a critical role in its biological function.
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Fels Institute for Cancer Research and Molecular Biology, Philadelphia, Pennsylvania 19140, USA.
Reddy
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D000818:Animals; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D051379:Mice; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020598:Proto-Oncogene Proteins c-myb; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C499306:Mybl2 protein, mouse; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D015534:Trans-Activators; D014157:Transcription Factors