title: GCUNC45 is the first Hsp90 co-chaperone to show alpha/beta isoform specificity.
abstract: Hsp90 is an essential molecular chaperone required for the normal functioning of many key regulatory proteins in eukaryotic cells. Vertebrates have two closely related isoforms of cytosolic Hsp90 (Hsp90alpha and Hsp90beta). However, specific functions for each isoform are largely unknown, and no Hsp90 co-chaperone has been reported to distinguish between the two isoforms. In this study, we show that the Hsp90 co-chaperone GCUNC45 bound preferentially to the beta isoform of Hsp90 in vitro. GCUNC45 efficiently blocked the progression of progesterone receptor chaperoning in an in vitro functional system when Hsp90beta was used, but did so with much less efficacy when Hsp90alpha was used. Knockdown experiments in HeLa cells showed that GCUNC45 is required for the normal cellular distribution of Hsp90beta, but not Hsp90alpha. This is the first example of a co-chaperone with isoform selectivity, and this approach may open novel avenues to understanding the functional differences between Hsp90 isoforms.
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. chadli.ahmed@mayo.edu
authors.forename: Ahmed
authors.initials: A
authors.lastname: Chadli
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Felts
authors.forename: David O
authors.initials: DO
authors.lastname: Toft
mesh_terms: D000818:Animals; D020868:Gene Silencing; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D018411:Spodoptera; D013379:Substrate Specificity / Q000502:physiology
chemical_list: D018841:HSP90 Heat-Shock Proteins; C493165:HSP90AB1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D020033:Protein Isoforms; D011980:Receptors, Progesterone; C509158:UNC45A protein, human