CDK-INDEPENDENT ACTIVATION OF ESTROGEN-RECEPTOR BY CYCLIN D1

Both cyclin D1 and estrogens have an essential role in regulating prol iferation of breast epithelial cells. We show here a novel role for cy clin D1 in growth regulation of estrogen-responsive tissues by potenti ating transcription of estrogen receptor-regulated genes. Cyclin D1 me diates this activation independent of complex formation to a CDK partn er. Cyclin D1 activates estrogen receptor-mediated transcription in th e absence of estrogen and enhances transcription in its presence. The activation of estrogen receptor by cyclin D1 is not inhibited by anti- estrogens. A direct physical binding of cyclin D1 to the hormone bindi ng domain of the estrogen receptor results in an increased binding of the receptor to estrogen response element sequences, and upregulates e strogen receptor-mediated transcription. These results highlight a nov el role for cyclin D1 as a CDK-independent activator of the estrogen r eceptor.