NR AIWB
AU Newnam,G.P.; Wegrzyn,R.D.; Lindquist,S.L.; Chernoff,Y.O.
TI Antagonistic interactions between yeast chaperones Hsp104 and Hsp70 in prion curing
QU Molecular and Cellular Biology 1999 Feb; 19(2): 1325-33
PT journal article
AB 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.
MH Fungal Proteins/genetics/*metabolism; Gene Expression; Genes, Fungal; Heat-Shock Proteins/genetics/*metabolism; Heat-Shock Proteins 70/genetics/*metabolism; Prions/chemistry/genetics/*metabolism; Protein Conformation; Saccharomyces cerevisiae/genetics/*metabolism; Solubility; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Suppression, Genetic; Temperature
AD School of Biology, Georgia Institute of Technology, Atlanta, Georgia 30332-0230, USA
SP englisch
PO USA