Murine A-myb Gene Encodes a Transcription Factor, Which Cooperates with Ets-2 and Exhibits Distinctive Biochemical and Biological Activities from c-myb

The myb gene family consists of three members, named A-, B-, and c-myb, which encode nuclear proteins that bind to DNA and function as regulators of transcription. Our results show that murine A-myb is a poor transactivator of transcription compared with murine c-myb. Deletion of the COOH-terminal domain of A-Myb, or co-expression with Ets-2 resulted in increased transactivation potential. While ectopic overexpression of c-myb in 32Dcl3 cells results in a block to the ability of these cells to undergo terminal differentiation resulting in indefinite growth in granulocyte-colony-stimulating factor (G-CSF), similar overexpression of A-myb results in growth arrest and concomitant terminal differentiation of 32D cells into granulocytes. Co-expression of A-myb and ets-2 in these cells results in the restoration of the proliferative activity of the cells in G-CSF, but fails to induce a block to G-CSF-induced terminal differentiation. However, overexpression of the COOH-terminal deletion mutant of A-myb results in a block to G-CSF-induced differentiation of 32D cells, suggesting that the distinctive biological phenotypes produced by A-myb and c-myb genes are mediated by their COOH-terminal domains.