title: The cochaperone SGTA (small glutamine-rich tetratricopeptide repeat-containing protein alpha) demonstrates regulatory specificity for the androgen, glucocorticoid, and progesterone receptors.
abstract: Steroid hormone receptors are ligand-dependent transcription factors that require the ordered assembly of multichaperone complexes for transcriptional activity. Although heat shock protein (Hsp) 90 and Hsp70 are key players in this process, multiple Hsp70- and Hsp90-associated cochaperones associate with receptor-chaperone complexes to regulate receptor folding and activation. Small glutamine-rich tetratricopeptide repeat-containing protein alpha (SGTA) was recently characterized as an Hsp70 and Hsp90-associated cochaperone that specifically regulates androgen receptor activity. However, the specificity of SGTA for additional members of the steroid hormone receptor superfamily and the mechanism by which SGTA regulates receptor activity remain unclear. Here we report that SGTA associates with and specifically regulates the androgen, glucocorticoid, and progesterone receptors and has no effect on the mineralocorticoid and estrogen receptors in both yeast and mammalian cell-based reporter assays. In both systems, SGTA knockdown/deletion enhances receptor activity, whereas SGTA overexpression suppresses receptor activity. We demonstrate that SGTA binds directly to Hsp70 and Hsp90 in vitro with similar affinities yet predominately precipitates with Hsp70 from cell lysates, suggesting a role for SGTA in early, Hsp70-mediated folding. Furthermore, SGTA expression completely abrogates the regulation of receptor function by FKBP52 (52-kDa FK506-binding protein), which acts at a later stage of the chaperone cycle. Taken together, our data suggest a role for SGTA at distinct steps in the chaperone-dependent modulation of androgen, glucocorticoid, and progesterone receptor activity.
authors.affiliation: From the Border Biomedical Research Center and Department of Biological Sciences and.
authors.forename: Atanu
authors.initials: A
authors.lastname: Paul
authors.affiliation: From the Border Biomedical Research Center and Department of Biological Sciences and.
authors.forename: Yenni A
authors.initials: YA
authors.lastname: Garcia
authors.affiliation: the Center for Integrated Protein Science at the Department Chemie, Technische Universität München, Garching, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Zierer
authors.affiliation: the Cancer Research Center, Georgia Regents University, Augusta, Georgia 30912, and.
authors.forename: Chaitanya
authors.initials: C
authors.lastname: Patwardhan
authors.affiliation: From the Border Biomedical Research Center and Department of Biological Sciences and.
authors.forename: Omar
authors.initials: O
authors.lastname: Gutierrez
authors.affiliation: the Department of Chemistry, University of Texas at El Paso, El Paso, Texas 79968.
authors.forename: Zacariah
authors.initials: Z
authors.lastname: Hildenbrand
authors.affiliation: From the Border Biomedical Research Center and Department of Biological Sciences and.
authors.forename: Diondra C
authors.initials: DC
authors.lastname: Harris
authors.affiliation: From the Border Biomedical Research Center and Department of Biological Sciences and.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Balsiger
authors.affiliation: From the Border Biomedical Research Center and Department of Biological Sciences and.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Sivils
authors.affiliation: the Department of Biological Sciences, University of Idaho, Moscow, Idaho 83844.
authors.forename: Jill L
authors.initials: JL
authors.lastname: Johnson
authors.affiliation: the Center for Integrated Protein Science at the Department Chemie, Technische Universität München, Garching, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Buchner
authors.affiliation: the Cancer Research Center, Georgia Regents University, Augusta, Georgia 30912, and.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Chadli
authors.affiliation: From the Border Biomedical Research Center and Department of Biological Sciences and mbcox@utep.edu.
authors.forename: Marc B
authors.initials: MB
authors.lastname: Cox
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D011944:Receptors, Androgen / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D022021:Tacrolimus Binding Proteins / Q000378:metabolism; D020798:Two-Hybrid System Techniques
chemical_list: D002352:Carrier Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; D011944:Receptors, Androgen; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; C114575:SGTA protein, human; D029701:Saccharomyces cerevisiae Proteins; C520576:Sgt2 protein, S cerevisiae; D022021:Tacrolimus Binding Proteins; C403485:tacrolimus binding protein 4
keywords: Androgen Receptor; Cochaperone; FKBP52; Glucocorticoid Receptor; Heat Shock Protein 90 (Hsp90); Hsp70; Progesterone; Prostate Cancer; SGTA; Steroid Hormone Receptor
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