p53 down-regulates ER-responsive genes by interfering with the binding of ER to ERE

Overexpression of the tumor suppressor p53 in HeLa cells leads to loss of t he estradiol- and genistein-induced human estrogen receptor (ER alpha) tran sactivity. The coactivator p300, which binds to both ERa and p53, does not prevent this loss of hER alpha function. In this report we demonstrate that p53 physically binds to multiple domains of the hERa. This binding did not interfere with either the ER alpha dimerization or the interaction between hER alpha and its coactivator SRC-1. However, p53 did interfere with the h ER alpha-ERE binding. These results may explain how p53 downregulates the e xpression of some estrogen-responsive genes such as c-fos, c-jun, TPA, and bcl-2. This study supports the cross-talk between the p53 and the ER alpha signaling pathways. (C) 1999 Academic Press.