No abstract

Estrogen receptor a (ERa) is a ligand-activated transcription factor that regulates expression of estrogen-responsive genes. Upon binding of the ligand-occupied ERa to estrogen response elements (EREs) in DNA, the receptor interacts with a variety of coregulatory proteins to modulate transcription of target genes. We have isolated and identified a number of proteins associated with the DNA-bound ERa. One of these proteins, Rho guanosine diphosphate (GDP) dissociation inhibitor a (RhoGDIa), is a negative regulator of the Rho family of GTP-binding proteins. In this study, we demonstrate that endogenously expressed RhoGDIa is present in the nucleus as well as the cytoplasm of MCF-7 breast cancer cells, and that RhoGDIa binds directly to ERa, alters the ERa-ERE interaction, and influences the ability of ERa to regulate transcription of a heterologous estrogen-responsive reporter plasmid in transient transfection assays as well as endogenous, estrogen-responsive genes in MCF-7 cells. Our studies suggest that, in addition to the activity of RhoGDIa in the cytoplasm, it also influences ERa signaling in the nucleus.