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Departments of ¹ Cell and Developmental Biology and ² Biochemistry,, University of Illinois, Urbana, Illinois 61801, USA ³ Department of Molecular and Integrative Physiology,, University of Illinois at Urbana-Champaign, 524 Burrill Hall, 407 South Goodwin Avenue, Urbana, Illinois 61801, USA ⁴ Department of Cell Biology,, The Scripps Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA

(Correspondence should be addressed to A M Nardulli; Email: anardull{at}life.uiuc.edu)

Estrogen receptor (ER) is a ligand-activated transcription factor that regulates expression of estrogen-responsive genes. Upon binding of the ligand-occupied ER 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 ER. One of these proteins, Rho guanosine diphosphate (GDP) dissociation inhibitor (RhoGDI), is a negative regulator of the Rho family of GTP-binding proteins. In this study, we demonstrate that endogenously expressed RhoGDI is present in the nucleus as well as the cytoplasm of MCF-7 breast cancer cells, and that RhoGDI binds directly to ER, alters the ER–ERE interaction, and influences the ability of ER 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 RhoGDI in the cytoplasm, it also influences ER signaling in the nucleus.

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				A. K. Rao, Y. S. Ziegler, I. X. McLeod, J. R. Yates, and A. M. Nardulli Effects of Cu/Zn Superoxide Dismutase on Estrogen Responsiveness and Oxidative Stress in Human Breast Cancer Cells Mol. Endocrinol., May 1, 2008; 22(5): 1113 - 1124. [Abstract] [Full Text] [PDF]