A Role for Cytosolic Hsp70 in Yeast [PSI⁺] Prion Propagation and [PSI⁺] as a Cellular Stress

Corresponding author: Daniel C. Masison, Bldg. 8, Rm. 407, 8 Center Dr., MSC 0851, National Institutes of Health, Bethesda, MD 20892-0851., masisond{at}helix.nih.gov (E-mail)

Communicating editor: A. P. MITCHELL

[PSI⁺] is a prion (infectious protein) of Sup35p, a subunit of the Saccharomyces cerevisiae translation termination factor. We isolated a dominant allele, SSA1-21, of a gene encoding an Hsp70 chaperone that impairs [PSI⁺] mitotic stability and weakens allosuppression caused by [PSI⁺]. While [PSI⁺] stability is normal in strains lacking SSA1, SSA2, or both, SSA1-21 strains with a deletion of SSA2 cannot propagate [PSI⁺]. SSA1-21 [PSI⁺] strains are hypersensitive to curing of [PSI⁺] by guanidine-hydrochloride and partially cured of [PSI⁺] by rapid induction of the heat-shock response but not by growth at 37°. The number of inheritable [PSI⁺] particles is significantly reduced in SSA1-21 cells. SSA1-21 effects on [PSI⁺] appear to be independent of Hsp104, another stress-inducible protein chaperone known to be involved in [PSI⁺] propagation. We propose that cytosolic Hsp70 is important for the formation of Sup35p polymers characteristic of [PSI⁺] from preexisting material and that Ssa1-21p both lacks and interferes with this activity. We further demonstrate that the negative effect of heat stress on [PSI⁺] phenotype directly correlates with solubility of Sup35p and find that in wild-type strains the presence of [PSI⁺] causes a stress that elevates basal expression of Hsp104 and SSA1.

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