title: Relationship between glucocorticoid receptor steroid-binding capacity and association of the Mr 90,000 heat shock protein with the unliganded receptor.
abstract: Treatment of rat liver cytosol with hydrogen peroxide (H2O2) or sodium molybdate (MoO4(2-)) inhibits thermal inactivation of glucocorticoid receptor steroid-binding capacity at 25 degrees C. Dithiothreitol (DTT) prevents the stabilization of receptors by H2O2. Heating (25 degrees C) of immune pellets formed by immunoadsorption of L-cell murine glucocorticoid receptor complexes to protein-A-Sepharose with an anti-receptor monoclonal antibody (BuGR2) results in dissociation of the M 90,000 heat shock protein (hsp90) from the steroid binding protein. Such thermal-induced dissociation of hsp90 is inhibited by H2O2. Pretreatment of immunoadsorbed receptor complexes with the thiol derivatizing agent, methyl methanethiosulfonate (MMTS) prevents the ability of H2O2 to stabilize the hsp90-receptor interaction. These data suggest a role for hsp90 in maintaining an active steroid-binding conformation of the glucocorticoid receptor.
authors.affiliation: Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109.
authors.forename: E H
authors.initials: EH
authors.lastname: Bresnick
authors.forename: E R
authors.initials: ER
authors.lastname: Sanchez
authors.forename: W B
authors.initials: WB
authors.lastname: Pratt
mesh_terms: D000818:Animals; D003600:Cytosol / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000302:isolation & purification / Q000378:metabolism*; D008024:Ligands; D008099:Liver / Q000378:metabolism*; D008297:Male; D008970:Molecular Weight; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000302:isolation & purification / Q000378:metabolism*; D014222:Triamcinolone Acetonide / Q000378:metabolism
chemical_list: D006360:Heat-Shock Proteins; D008024:Ligands; D011965:Receptors, Glucocorticoid; D014222:Triamcinolone Acetonide