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Molecular and Cellular Biology, February 1999, p. 1325-1333, Vol. 19, No. 2
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Antagonistic Interactions between Yeast Chaperones Hsp104 and Hsp70 in Prion Curing

Gary P. Newnam,1 Renee D. Wegrzyn,1 Susan L. Lindquist,2 and Yury O. Chernoff1,*

School of Biology, Georgia Institute of Technology, Atlanta, Georgia 30332-0230,1 and Howard Hughes Medical Institute and Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, Illinois 606372

Received 19 August 1998/Returned for modification 23 September 1998/Accepted 26 October 1998

The maintenance of [PSI], a prion-like form of the yeast release factor Sup35, requires a specific concentration of the chaperone protein Hsp104: either deletion or overexpression of Hsp104 will cure cells of [PSI]. A major puzzle of these studies was that overexpression of Hsp104 alone, from a heterologous promoter, cures cells of [PSI] very efficiently, yet the natural induction of Hsp104 with heat shock, stationary-phase growth, or sporulation does not. These observations pointed to a mechanism for protecting the genetic information carried by the [PSI] element from vicissitudes of the environment. Here, we show that simultaneous overexpression of Ssa1, a protein of the Hsp70 family, protects [PSI] from curing by overexpression of Hsp104. Ssa1 protein belongs to the Ssa subfamily, members of which are normally induced with Hsp104 during heat shock, stationary-phase growth, and sporulation. At the molecular level, excess Ssa1 prevents a shift of Sup35 protein from the insoluble (prion) to the soluble (cellular) state in the presence of excess Hsp104. Overexpression of Ssa1 also increases nonsense suppression by [PSI] when Hsp104 is expressed at its normal level. In contrast, hsp104 deletion strains lose [PSI] even in the presence of overproduced Ssa1. Overproduction of the unrelated chaperone protein Hsp82 (Hsp90) neither cured [PSI] nor antagonized the [PSI]-curing effect of overproduced Hsp104. Our results suggest it is the interplay between Hsp104 and Hsp70 that allows the maintenance of [PSI] under natural growth conditions.

* Corresponding author. Mailing address: School of Biology, Georgia Institute of Technology, 310 Ferst Dr., Room 303, Atlanta, GA 30332-0230. Phone: (404) 894-1157. Fax: (404) 894-0519. E-mail: yc22{at}prism.gatech.edu.

Molecular and Cellular Biology, February 1999, p. 1325-1333, Vol. 19, No. 2
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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