The cochaperone SGTA (small glutamine-rich tetratricopeptide repeat-containing protein alpha) demonstrates regulatory specificity for the androgen, glucocorticoid, and progesterone receptors

Atanu Paul; Yenni A Garcia; Bettina Zierer; Chaitanya Patwardhan; Omar Gutierrez; Zacariah Hildenbrand; Diondra C Harris; Heather A Balsiger; Jeffrey C Sivils; Jill L Johnson; Johannes Buchner; Ahmed Chadli; Marc B Cox

doi:10.1074/jbc.M113.535229

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The cochaperone SGTA (small glutamine-rich tetratricopeptide repeat-containing protein alpha) demonstrates regulatory specificity for the androgen, glucocorticoid, and progesterone receptors

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The cochaperone SGTA (small glutamine-rich tetratricopeptide repeat-containing protein alpha) demonstrates regulatory specificity for the androgen, glucocorticoid, and progesterone receptors

Atanu Paul, Yenni A Garcia, Bettina Zierer, Chaitanya Patwardhan, Omar Gutierrez, Zacariah Hildenbrand, Diondra C Harris, Heather A Balsiger, Jeffrey C Sivils, Jill L Johnson, …

The Journal of biological chemistry, Vol.289(22), pp.15297-15308

05/30/2014

DOI: https://doi.org/10.1074/jbc.M113.535229

Handle:

https://hdl.handle.net/2376/114152

PMCID: PMC4140887

PMID: 24753260

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https://doi.org/10.1074/jbc.M113.535229View

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Abstract

Amino Acid Sequence

Molecular Chaperones - metabolism

Saccharomyces cerevisiae - genetics

Humans

Receptors, Androgen - metabolism

Molecular Chaperones - genetics

Molecular Sequence Data

HSP70 Heat-Shock Proteins - genetics

Receptors, Glucocorticoid - metabolism

Tacrolimus Binding Proteins - metabolism

Saccharomyces cerevisiae Proteins - genetics

Gene Knockdown Techniques

HSP70 Heat-Shock Proteins - metabolism

Receptors, Progesterone - metabolism

Saccharomyces cerevisiae - metabolism

Carrier Proteins - genetics

Two-Hybrid System Techniques

Carrier Proteins - metabolism

Saccharomyces cerevisiae Proteins - metabolism

HSP90 Heat-Shock Proteins - metabolism

HSP90 Heat-Shock Proteins - genetics

HeLa Cells

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.

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Title: The cochaperone SGTA (small glutamine-rich tetratricopeptide repeat-containing protein alpha) demonstrates regulatory specificity for the androgen, glucocorticoid, and progesterone receptors
Creators: Atanu Paul - From the Border Biomedical Research Center and Department of Biological Sciences and
Yenni A Garcia - From the Border Biomedical Research Center and Department of Biological Sciences and
Bettina Zierer - the Center for Integrated Protein Science at the Department Chemie, Technische Universität München, Garching, Germany
Chaitanya Patwardhan - the Cancer Research Center, Georgia Regents University, Augusta, Georgia 30912, and
Omar Gutierrez - From the Border Biomedical Research Center and Department of Biological Sciences and
Zacariah Hildenbrand - the Department of Chemistry, University of Texas at El Paso, El Paso, Texas 79968
Diondra C Harris - From the Border Biomedical Research Center and Department of Biological Sciences and
Heather A Balsiger - From the Border Biomedical Research Center and Department of Biological Sciences and
Jeffrey C Sivils - From the Border Biomedical Research Center and Department of Biological Sciences and
Jill L Johnson - the Department of Biological Sciences, University of Idaho, Moscow, Idaho 83844
Johannes Buchner - the Center for Integrated Protein Science at the Department Chemie, Technische Universität München, Garching, Germany
Ahmed Chadli - the Cancer Research Center, Georgia Regents University, Augusta, Georgia 30912, and
Marc B Cox - From the Border Biomedical Research Center and Department of Biological Sciences and mbcox@utep.edu
Publication Details: The Journal of biological chemistry, Vol.289(22), pp.15297-15308
Academic Unit: UNKNOWN
Publisher: United States
Grant note: R01 GM102443-01 / NIGMS NIH HHS G12 MD007592 / NIMHD NIH HHS 5 G12 RR008124 / NCRR NIH HHS R01 GM102443 / NIGMS NIH HHS SC1GM084863 / NIGMS NIH HHS G12 RR008124 / NCRR NIH HHS SC1 GM084863 / NIGMS NIH HHS 8 G12 MD007592 / NIMHD NIH HHS
Identifiers: 99900547458101842
Language: English
Resource Type: Journal article