D-type cyclins complex with the androgen receptor and inhibit its transcriptional transactivation ability

D-type cyclins regulate distinct cellular processes, such as mitotic cell c ycle control, differentiation, and transcription. We have previously shown that the D-type cyclins are critical for the androgen-dependent proliferati on of prostate cells. Here, we sought to determine whether cyclin D1 direct ly influences the transactivation potential of the androgen receptor, a tra nscription factor that strongly influences androgen-dependent proliferation . We found that Ligand-mediated transcriptional activation of a physiologic al target, prostate-specific antigen, by the androgen receptor was inhibite d by cyclins D1 and D3. The ability of D-type cyclins to inhibit androgen r eceptor transactivation was not shared with other cyclins, and cyclin D1 wa s as effective as dominant negative mutants of the androgen receptor in inh ibiting transactivation. This function of cyclin D1 was independent of its role in cell cycle progression and is likely elicited through its ability t o form a specific complex with the androgen receptor. These data underscore the various mechanisms through which the androgen receptor is regulated an d also point to a negative feedback role for cyclin D1 in controlling andro gen-dependent growth.