Regulation of Estrogen Receptor-Dependent Transcriptional Activation by a Cyclin-Dependent Kinase

摘要

The estrogen receptor a is transcription factor that is regulated by ligand binding and phosphorylation. The phosphorylation of three serine residues (S104, S106 and S118) located within the N-terminal transcriptional activation domain (AF- 1) of the receptor are important for full receptor transcriptional activation. We provide evidence that alteration in the regulation of cyclinA/ cdk2 complex lead to changes in hormone-dependent and hormone-independent transcriptional enhancement by ER This is accomplished, at least in part, through the direct phosphorylation of ER S104, S106 and S118 by the cyclinA/Cdk2 complex. Since alterations in cydin dependent kinase regulatory proteins are a common feature in breast cancer, these findings provide a framework for understanding the mechanism by which CDK dysregulation can directly affect ER signaling through alterations in receptor phosphorylation.