title: Mutation of essential Hsp90 co-chaperones SGT1 or CNS1 renders yeast hypersensitive to overexpression of other co-chaperones.
abstract: The essential molecular chaperone Hsp90 functions with over ten co-chaperones in Saccharomyces cerevisiae, but the in vivo roles of many of these co-chaperones are poorly understood. Two of these co-chaperones, Cdc37 and Sgt1, target specific types of clients to Hsp90 for folding. Other co-chaperones have general roles in supporting Hsp90 function, but the degree of overlapping or competing functions is unclear. None of the chaperones, when overexpressed, were able to rescue the lethality of an SGT1 disruption strain. However, overexpression of SBA1, PPT1, AHA1 or HCH1 caused varying levels of growth defects in an sgt1-K360E strain. Negative effects of CPR6 overexpression were similarly observed in cells expressing the temperature-sensitive mutation cns1-G90D. In all cases, alterations within co-chaperones designed to disrupt Hsp90 interaction relieved the negative growth defects. Sgt1-K360E and Cns1-G90D were previously shown to exhibit reduced Hsp90 interaction. Our results indicate that overexpression of other co-chaperones further disrupts the essential functions of Cns1 and Sgt1. However, the specificity of the negative effects indicates that only a subset of co-chaperones competes with Sgt1 or Cns1 for binding to Hsp90. This provides new evidence that co-chaperones selectively compete for binding to subpopulations of cellular Hsp90 and suggest that changes in the relative levels of co-chaperones may have dramatic effects on Hsp90 function.
authors.affiliation: Department of Biological Sciences, University of Idaho, P.O. Box 443051, Moscow, ID, 83844-3051, USA, jilljohn@uidaho.edu.
authors.forename: Jill L
authors.initials: JL
authors.lastname: Johnson
authors.forename: Abbey D
authors.initials: AD
authors.lastname: Zuehlke
authors.forename: Victoria R
authors.initials: VR
authors.lastname: Tenge
authors.forename: Jordan C
authors.initials: JC
authors.lastname: Langworthy
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C116075:CNS1 protein, S cerevisiae; C074510:HSP82 protein, S cerevisiae; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; C470726:SGT1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins