PCAF associates with cyclin D1 and potentiates its activation of the estrogen receptor

Cyclin D1 is overexpressed in a significant percentage of human breast canc ers, particularly in those that also express the estrogen receptor (ER). We and others have demonstrated previously that experimentally overexpressed cyclin D1 can associate with the ER and stimulate its transcriptional funct ions in the absence of estrogen, This effect is separable from the establis hed function of cyclin D1 as a regulator of cyclin-dependent kinases. Here, we demonstrate that cyclin D1 can also interact with the histone acetyltra nsferase, p300/CREB-binding protein-associated protein (P/CAF), thereby fac ilitating an association between P/CAF and the ER. Ectopic expression of P/ CAF potentiates cyclin D1-stimulated ER activity in a dose-dependent manner . This effect is largely dependent on the acetyltransferase activity of P/C AF. These results suggest that cyclin D1 may trigger the activation of the ER through the recruitment of P/CAF, by providing histone acetyltransferase activity and, potentially, links to additional P/CAF-associated transcript ional coactivators.