McMahon C, Suthiphongchai T, DiRenzo J, Ewen M E
Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston MA 02115, USA.
Proc Natl Acad Sci U S A. 1999 May 11;96(10):5382-7. doi: 10.1073/pnas.96.10.5382.
Cyclin D1 is overexpressed in a significant percentage of human breast cancers, 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 functions in the absence of estrogen. This effect is separable from the established function of cyclin D1 as a regulator of cyclin-dependent kinases. Here, we demonstrate that cyclin D1 can also interact with the histone acetyltransferase, p300/CREB-binding protein-associated protein (P/CAF), thereby facilitating 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/CAF. 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 transcriptional coactivators.
细胞周期蛋白D1在相当比例的人类乳腺癌中过表达，尤其是在那些也表达雌激素受体（ER）的乳腺癌中。我们和其他人之前已经证明，实验性过表达的细胞周期蛋白D1可以与ER结合，并在没有雌激素的情况下刺激其转录功能。这种效应与细胞周期蛋白D1作为细胞周期蛋白依赖性激酶调节剂的既定功能是可分离的。在这里，我们证明细胞周期蛋白D1还可以与组蛋白乙酰转移酶p300/CREB结合蛋白相关蛋白（P/CAF）相互作用，从而促进P/CAF与ER之间的结合。P/CAF的异位表达以剂量依赖性方式增强细胞周期蛋白D1刺激的ER活性。这种效应很大程度上依赖于P/CAF的乙酰转移酶活性。这些结果表明，细胞周期蛋白D1可能通过招募P/CAF来触发ER的激活，通过提供组蛋白乙酰转移酶活性，并可能与其他P/CAF相关的转录共激活因子建立联系。
