title: The ribosomal biogenesis protein Utp21 interacts with Hsp90 and has differing requirements for Hsp90-associated proteins.
abstract: The molecular chaperone Hsp90 buffers the effects of genetic variation by assisting the stabilization and folding of multiple clients critical for cell signaling and growth. We identified an interaction of Hsp90 and associated proteins with the essential nucleolar protein, Utp21, part of a large complex required for biogenesis of the small ribosomal subunit. The utp21-S602F mutation, which causes minor defects in otherwise wild-type yeast, exhibited severe or lethal growth defects when combined with mutations in Hsp90 or co-chaperones. WT Utp21 and Utp21-S602F exhibited similar interactions with Hsp90, and steady-state levels of WT Utp21 were reduced upon Hsp90 mutation or inhibition. Mutations in the human homolog of UTP21, WDR36, have been associated with adult-onset primary open-angle glaucoma, a leading cause of blindness worldwide. Three different mutant forms of Utp21 analogous to glaucoma-associated WDR36 mutations exhibit reduced levels in yeast cells expressing mutations in Hsp90 or associated chaperones, suggesting that Hsp90 and co-chaperones buffer the effects of those mutations.
authors.affiliation: Department of Biological Sciences and the Center for Reproductive Biology, University of Idaho, Moscow, Idaho, United States of America.
authors.forename: Victoria R
authors.initials: VR
authors.lastname: Tenge
authors.affiliation: Department of Biological Sciences and the Center for Reproductive Biology, University of Idaho, Moscow, Idaho, United States of America.
authors.forename: Jared
authors.initials: J
authors.lastname: Knowles
authors.affiliation: Department of Biological Sciences and the Center for Reproductive Biology, University of Idaho, Moscow, Idaho, United States of America.
authors.forename: Jill L
authors.initials: JL
authors.lastname: Johnson
mesh_terms: D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D015151:Immunoblotting; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018841:HSP90 Heat-Shock Proteins; D009687:Nuclear Proteins; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; C531337:Utp21 protein, S cerevisiae