title: Global functional map of the p23 molecular chaperone reveals an extensive cellular network.
abstract: In parallel with evolutionary developments, the Hsp90 molecular chaperone system shifted from a simple prokaryotic factor into an expansive network that includes a variety of cochaperones. We have taken high-throughput genomic and proteomic approaches to better understand the abundant yeast p23 cochaperone Sba1. Our work revealed an unexpected p23 network that displayed considerable independence from known Hsp90 clients. Additionally, our data uncovered a broad nuclear role for p23, contrasting with the historical dogma of restricted cytosolic activities for molecular chaperones. Validation studies demonstrated that yeast p23 was required for proper Golgi function and ribosome biogenesis, and was necessary for efficient DNA repair from a wide range of mutagens. Notably, mammalian p23 had conserved roles in these pathways as well as being necessary for proper cell mobility. Taken together, our work demonstrates that the p23 chaperone serves a broad physiological network and functions both in conjunction with and sovereign to Hsp90.
authors.affiliation: Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, 601 S. Goodwin Avenue, Urbana, IL 61801, USA.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Echtenkamp
authors.forename: Elena
authors.initials: E
authors.lastname: Zelin
authors.forename: Ellinor
authors.initials: E
authors.lastname: Oxelmark
authors.forename: Joyce I
authors.initials: JI
authors.lastname: Woo
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Andrews
authors.forename: Michael
authors.initials: M
authors.lastname: Garabedian
authors.forename: Brian C
authors.initials: BC
authors.lastname: Freeman
mesh_terms: D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004260:DNA Repair / Q000502:physiology; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; C113025:SBA1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins