By-pass of TPA-induced differentiation and cell cycle arrest by the c-Myb DNA-binding domain.

Monoblasts transformed by v-Myb can be induced to differentiate into macrophages by treatment with phorbol ester (TPA). This differentiation occurs during both the G1 and the G2 phases of the cell cycle and is accompanied by cell cycle arrest. The introduction of a protein consisting of the three repeats (3R) of the c-Myb DNA-binding domain permits the by-pass of this phorbol ester-induced differentiation and cell cycle arrest. In particular, monoblasts which express the 3R protein progress through both the G1/S and G2/M transitions in the presence of phorbol ester. However, the 3R protein contains no detectable transcriptional activation domain. These results demonstrate that the c-Myb DNA-binding domain can regulate the cell cycle without functioning as a direct transcriptional activator.