[PSI+] is a prion (infectious protein) of Sup35p, a subunit of the translation termination factor, and [URE3] is a prion of Ure2p, a mediator of nitrogen catabolite repression. Here, we trace the history of these prions and describe the array of anti-prion systems in S. cerevisiae. These systems work together to block prion infection, prion generation, prion propagation, prion segregation, and the lethal (and near-lethal) effects of most variants of these prions. Each system lowers the appearance of prions 2- to 15-fold, but together, ribosome-associated chaperones, the Hsp104 disaggregase, and the Sup35p-binding Upf proteins lower the frequency of [PSI+] appearance by ~5000-fold. [PSI+] variants can be categorized by their sensitivity to the various anti-prion systems, with the majority of prion isolates sensitive to all three of the above-mentioned systems. Yeast prions have been used to screen for human anti-prion proteins, and five of the Bag protein family members each have such activity. We suggest that manipulation of human anti-prion systems may be useful in preventing or treating some of the many human amyloidoses currently found to be prions with the same amyloid architecture as the yeast prions.

• PMID: 40130511
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Journal Article | Review

Authors

Wickner RB, Hayashi Y, Edskes HK

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