Striatin-3 gamma inhibits estrogen receptor activity by recruiting a protein phosphatase.
A splicing variant of rat striatin-3 (rSTRN3gamma) was found to associate with estrogen receptor-alpha (ERalpha) in a ligand-dependent manner. In two-hybrid and pull-down analyses, estradiol induced an interaction between rSTRN3gamma and ERalpha. STRN3gamma protein was found in nuclear extracts from rat uterus and human cell lines. Overexpression of rSTRN3gamma induced a decrease in ERalpha transcriptional activity but had no effect on ERbeta activity. Immunoprecipitation analyses showed that rSTRN3gamma interacts with both the ERalpha and the catalytic subunit of protein phosphatase 2A (PP2A(C)). The transrepressor action of rSTRN3gamma was overcome by okadaic acid, an inhibitor of PP2A(C), and by cotransfection of PP2A(C) siRNA. rSTRN3gamma caused dephosphorylation of ERalpha at serine 118 and this was abrogated by okadaic acid. ERalpha lacking phosphorylation sites at either serine 118 or 167 was insensitive to the corepressor action of rSTRN3gamma. These observations suggest that an rSTRN3gamma-PP2A(C) complex is recruited to agonist-activated ERalpha, thereby leading to its dephosphorylation and inhibiting transcription.
Tan
Bailin
B
Department of Obstetrics and Gynecology University School of Medicine, Indianapolis, Indiana 46202, USA.
Long
Xinghua
X
Nakshatri
Harikrishna
H
Nephew
Kenneth P
KP
Bigsby
Robert M
RM
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000502:physiology*; D019556:COS Cells; D002148:Calmodulin-Binding Proteins / Q000502:physiology*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004965:Estrogen Antagonists / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D020033:Protein Isoforms / Q000502:physiology; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D051381:Rats; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*
D001324:Autoantigens; D002148:Calmodulin-Binding Proteins; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D020033:Protein Isoforms; D011960:Receptors, Estrogen; C405682:STRN3 protein, human; C485774:Strn3 protein, rat; D054648:Protein Phosphatase 2