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Mol. Cell. Biol., Jan 1998, 499-511, Vol 18, No. 1
IH Oh and EP Reddy
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.
Copyright © 1998, American Society for Microbiology
The C-terminal domain of B-Myb acts as a positive regulator of transcription and modulates its biological functions
Fels Institute for Cancer Research and Molecular Biology, Philadelphia, Pennsylvania 19140, USA.
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