Prions are infectious
protein isoforms, which are believed to reproduce themselves by
converting the normal protein into a prion form. Yeast prion [PSI] is an
aggregation-prone isoform of the translational termination factor Sup35
(eRF3). Previously, we have shown that inactivation or overproduction of
the chaperone protein Hsp104 cures cells of [PSI] (Chernoff et al.,
Science, 268: 880, 1995). Here, we show that Hsp70 chaperones modify
Hsp104 effect on [PSI]. Our data explain why [PSI] isn't cured by growth
at high temperature when both Hsp104 and some members of Hsp70 family
are induced. We also show that Sla1 protein, which is normally assisting
in nucleation of the cortical cytoskeletal microfilaments, interacts to
the Sup35 prion-forming domain in the two-hybrid system. Nonsense-suppression caused by overproduction of the Sup35 derivatives, as well
as formation and propagation of [PSI] prion, are affected in the strains
lacking Sla1. It appears that prion formation and propagation is
regulated by interactions between the Sup35 and its protein partners. We
suggest that prion appearance is a by-product of the processes, which
are involved in protein localization and are assisted by chaperones and
cytoskeletal networks.(This work was supported in part by the NIH grant
R21GM55091 to Y.O.C.)
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