D‐type cyclins repress transcriptional activation by the v‐Myb but not the c‐Myb DNA‐binding domain

The v‐Myb DNA‐binding domain differs from that of c‐Myb mainly by deletion of the first of three repeats. This truncation correlates with efficient oncogenic transformation and a decrease in DNA‐binding activity. Here we demonstrate that the D‐type cyclins, cyclin D1 and D2 in particular, specifically inhibit transcription when activated through the v‐Myb DNA‐binding domain, but not the c‐Myb DNA‐binding domain. Analysis of a cyclin D1 mutant and a dominant‐negative CDK4 mutant implied that this repression is independent of complex formation with a CDK partner. Association of cyclin D1 and D2 with the Myb DNA‐binding domain could be demonstrated. Increased levels of cyclin D1 and D2 resulted in a stabilization of the Myb proteins, but not in an alteration in binding of the Myb proteins to DNA. These results highlight an unexpected role for cyclin D as a CDK‐independent repressor of transcriptional activation by v‐Myb but not c‐Myb. This differential effect of D‐type cyclins on v‐Myb and c‐Myb might help to explain the mechanism underlying the oncogenic activity of v‐Myb, which appears to be a stronger transcriptional activator following the TPA‐induced differentiation of transformed monoblasts when cyclin D1 and D2 are down‐regulated.