- Made available online as an Accepted Preprint 19 February 2008
- Accepted Preprint first posted online on 19 February 2008
Striatin-3γ inhibits estrogen receptor activity by recruiting a protein phosphatase
- Department of Obstetrics and Gynecology University School of Medicine, 975 West Walnut Street (IB360), Indianapolis, Indiana 46202, USA1Department of Medical Sciences Program, Indiana University School of Medicine, Bloomington, Indianapolis, Indiana 47405, USA2Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
- (Correspondence should be addressed to R M Bigsby; Email: rbigsby{at}iupui.edu)
Abstract
A splicing variant of rat striatin-3 (rSTRN3γ) was found to associate with estrogen receptor-α (ERα) in a ligand-dependent manner. In two-hybrid and pull-down analyses, estradiol induced an interaction between rSTRN3γ and ERα. STRN3γ protein was found in nuclear extracts from rat uterus and human cell lines. Overexpression of rSTRN3γ induced a decrease in ERα transcriptional activity but had no effect on ERβ activity. Immunoprecipitation analyses showed that rSTRN3γ interacts with both the ERα and the catalytic subunit of protein phosphatase 2A (PP2A(C)). The transrepressor action of rSTRN3γ was overcome by okadaic acid, an inhibitor of PP2A(C), and by cotransfection of PP2A(C) siRNA. rSTRN3γ caused dephosphorylation of ERα at serine 118 and this was abrogated by okadaic acid. ERα lacking phosphorylation sites at either serine 118 or 167 was insensitive to the corepressor action of rSTRN3γ. These observations suggest that an rSTRN3γ-PP2A(C) complex is recruited to agonist-activated ERα, thereby leading to its dephosphorylation and inhibiting transcription.
- Revision received 24 January 2008
- Accepted 19 February 2008
- © 2008 Society for Endocrinology
