Estrogen receptor protects p53 from deactivation by human double minute-2

We and others have demonstrated that estrogen receptor or (ER alpha) and p5 3, two important regulatory proteins in breast cancer, bind to each other. In this report, using the glutathione S-transferase pull-down methodology, we show the ligand-independent interaction of ERa with the NH2-terminal reg ion of p53, a region known to bind the p300 and human double minute-2 (hdm2 ) regulatory factors. Furthermore, we have demonstrated that ER alpha is ca pable of binding hdm2 directly. The interaction of ER alpha and p53 does no t interfere with the binding between p53 and hdm2; rather, these proteins f orm a ternary complex, The effect of ER alpha on the p53-hdm2 regulatory lo op has been examined. Our results indicate that ER alpha protects p53 from being deactivated by hdm2, It is evident from these investigations that the ligand-independent protection of p53 by ER alpha is a novel role for this protein in addition to its classic regulatory function as a ligand-inducibl e transcription factor. This study also describes a new mechanism of cellul ar regulation of p53 activity.