Moosavi, Behrooz and Wongwigkarn, Jintana and Tuite, M.F. (2010) Hsp70/Hsp90 co-chaperones are required for efficient Hsp104-mediated elimination of the yeast [PSI+] prion but not for prion propagation. Yeast, 27 (3). pp. 167-179. ISSN 0749-503X.
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he 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 (hsp104K218T/K620T) or a ‘trap’ mutant Hsp104 (hsp104E285Q/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.
|Divisions:||Faculties > Science Technology and Medical Studies > School of Biosciences|
|Depositing User:||Sue Davies|
|Date Deposited:||28 Mar 2012 13:26|
|Last Modified:||03 Apr 2012 10:35|
|Resource URI:||http://kar.kent.ac.uk/id/eprint/29221 (The current URI for this page, for reference purposes)|
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