期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2017
卷号：114
期号：21
页码：E4193-E4202
DOI：10.1073/pnas.1704016114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Overproduction or deficiency of many chaperones and other cellular components cure the yeast prions [ PSI +] (formed by Sup35p) or [ URE3 ] (based on Ure2p). However, at normal expression levels, Btn2p and Cur1p eliminate most newly arising [ URE3 ] variants but do not cure [ PSI +], even after overexpression. Deficiency or overproduction of Hsp104 cures the [ PSI +] prion. Hsp104 deficiency curing is a result of failure to cleave the Sup35p amyloid filaments to make new seeds, whereas Hsp104 overproduction curing occurs by a different mechanism. Hsp104(T160M) can propagate [ PSI +], but cannot cure it by overproduction, thus separating filament cleavage from curing activities. Here we show that most [ PSI +] variants arising spontaneously in an hsp104(T160M) strain are cured by restoration of just normal levels of the WT Hsp104. Both strong and weak [ PSI +] variants are among those cured by this process. This normal-level Hsp104 curing is promoted by Sti1p, Hsp90, and Sis1p, proteins previously implicated in the Hsp104 overproduction curing of [ PSI +]. The [ PSI +] prion arises in hsp104(T160M) cells at more than 10-fold the frequency in WT cells. The curing activity of Hsp104 thus constitutes an antiprion system, culling many variants of the [ PSI +] prion at normal Hsp104 levels.
