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 D NA in a sequence-specific manner and function as regulators of transcr iption, In this report, we have examined the biochemical and biologica l activities of murine B-myb and compared these properties with those of murine c-myb, In transient transactivation assays, murine B-myb exh ibited transactivation potential comparable to that of c-myb. An analy sis of deletion mutants of B-myb and c-myb showed that while the C-ter minal domain of c-Myb acts as a negative regulator of transcriptional transactivation, the C-terminal domain of B-Myb functions as a positiv e enhancer of transactivation. To compare the biological activities of c-myb and B-myb, the two genes were overexpressed in 32Dc13 cells, wh ich are known to undergo terminal differentiation into granulocytes in the presence of granulocyte colony-stimulating factor (G-CSF), We obs erved that c-myb blocked the G-CSF-induced terminal differentiation of 32Dc13 cells, resulting in their continued proliferation in the prese nce 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 acce lerated the G-CSP-induced granulocytic differentiation of these cells, Similar studies with B-myb-c-myb chimeras showed that only chimeras t hat contained the C-terminal domain of B-Myb were able to accelerate t he G-CSF-induced terminal differentiation of 32Dc13 cells, These studi es show that c-myb and B-myb do not exhibit identical biological activ ities and that the carboxyl-terminal regulatory domain of B-Myb plays a critical role in its biological function.