A novel estrogen receptor α-associated protein alters receptor-deoxyribonucleic acid interactions and represses receptor-mediated transcription

Estrogen receptor alpha (ERalpha) serves as a ligand-activated transcription factor, turning on transcription of estrogen-responsive genes in target cells. Numerous regulatory proteins interact with the receptor to influence ERalpha-mediated transactivation. In this study, we have identified pp32, which interacts with the DNA binding domain of ERalpha when the receptor is free, but not when it is bound to an estrogen response element. Coimmunoprecipitation experiments demonstrate that endogenously expressed pp32 and ERalpha from MCF-7 breast cancer cells interact. Although pp32 substantially enhances the association of the receptor with estrogen response element-containing DNA, overexpression of pp32 in MCF-7 cells decreases transcription of an estrogen-responsive reporter plasmid. pp32 Represses p300-mediated acetylation of ERalpha and histones in vitro and inhibits acetylation of ERalpha in vivo. pp32 Also binds to other nuclear receptors and inhibits thyroid hormone receptor beta-mediated transcription. Taken together, our studies provide evidence that pp32 plays a role in regulating transcription of estrogen-responsive genes by modulating acetylation of histones and ERalpha and also influences transcription of other hormone-responsive genes as well.