Document Detail


Hsp70/Hsp90 co-chaperones are required for efficient Hsp104-mediated elimination of the yeast [PSI(+)] prion but not for prion propagation.
MedLine Citation:
PMID:  20014008     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The continued propagation of the yeast [PSI(+)] prion requires the molecular chaperone Hsp104 yet in cells engineered to overexpress Hsp104; prion propagation is impaired leading to the rapid appearance of prion-free [psi(-)] cells. The underlying mechanism of prion loss in such cells is unknown but is assumed to be due to the complete dissolution of the prion aggregates by the ATP-dependent disaggregase activity of this chaperone. To further explore the mechanism, we have sought to identify cellular factors required for prion loss in such cells. Sti1p and Cpr7p are co-chaperones that modulate the activity of Hsp70/Ssa and Hsp90 chaperones and bind to the C-terminus of Hsp104. Neither Sti1p nor Cpr7p is necessary for prion propagation but we show that deletion of the STI1 and CPR7 genes leads to a significant reduction in the generation of [psi(-)] cells by Hsp104 overexpression. Deletion of the STI1 and CPR7 genes does not modify the elimination of [PSI(+)] by guanidine hydrochloride, which inhibits the ATPase activity of Hsp104 but does block elimination of [PSI(+)] by overexpression of either an ATPase-defective mutant of Hsp104 (hsp104(K218T/K620T)) or a 'trap' mutant Hsp104 (hsp104(E285Q/E687Q)) that can bind its substrate but can not release it. These results provide support for the hypothesis that [PSI(+)] elimination by Hsp104 overexpression is not simply a consequence of complete dissolution of the prion aggregates but rather is through a mechanism distinct from the remodelling activity of Hsp104.
Authors:
Behrooz Moosavi; Jintana Wongwigkarn; Mick F Tuite
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Yeast (Chichester, England)     Volume:  27     ISSN:  1097-0061     ISO Abbreviation:  Yeast     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-02-26     Completed Date:  2010-05-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8607637     Medline TA:  Yeast     Country:  England    
Other Details:
Languages:  eng     Pagination:  167-79     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2009 John Wiley & Sons, Ltd.
Affiliation:
Kent Fungal Group, School of Biosciences, University of Kent, Canterbury, UK.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Substitution / genetics
Cyclophilins / genetics,  metabolism*
Gene Deletion
HSP70 Heat-Shock Proteins / genetics,  metabolism
HSP90 Heat-Shock Proteins / genetics,  metabolism
Heat-Shock Proteins / genetics,  metabolism*
Mutant Proteins / genetics,  metabolism
Mutation, Missense
Prions / metabolism*
Saccharomyces cerevisiae / genetics,  metabolism*
Saccharomyces cerevisiae Proteins / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/HSP70 Heat-Shock Proteins; 0/HSP82 protein, S cerevisiae; 0/HSP90 Heat-Shock Proteins; 0/Heat-Shock Proteins; 0/Mutant Proteins; 0/Prions; 0/SSA3 protein, S cerevisiae; 0/STI1 protein, S cerevisiae; 0/Saccharomyces cerevisiae Proteins; 143012-44-6/HsP104 protein, S cerevisiae; EC 5.2.1.-/Cyclophilins; EC 5.2.1.8/cyclophilin D

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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