title: Clearance of yeast eRF-3 prion [PSI+] by amyloid enlargement due to the imbalance between chaperone Ssa1 and cochaperone Sgt2.
abstract: The cytoplasmic [PSI+] element of budding yeast represents the prion conformation of translation release factor eRF-3 (Sup35). Prions are transmissible agents caused by self-seeded highly ordered aggregates (amyloids). Much interest lies in understanding how prions are developed and transmitted. However, the cellular mechanism involved in the prion clearance is unknown. Recently we have reported that excess misfolded multi-transmembrane protein, Dip5ΔC-v82, eliminates yeast prion [PSI+]. In this study, we showed that the prion loss was caused by enlargement of prion amyloids, unsuitable for transmission, and its efficiency was affected by the cellular balance between the chaperone Hsp70-Ssa1 and Sgt2, a small cochaperone known as a regulator of chaperone targeting to different types of aggregation-prone proteins. The present findings suggest that Sgt2 is titrated by excess Dip5ΔC-v82, and the shortage of Sgt2 led to non-productive binding of Ssa1 on [PSI+] amyloids. Clearance of prion [PSI+] by the imbalance between Ssa1 and Sgt2 might provide a novel array to regulate the release factor function in yeast.
authors.affiliation: Institute of Medical Science; University of Tokyo; Minato-ku, Tokyo, Japan; Department of Medical Genome Sciences; Graduate School of Frontier Sciences; The University of Tokyo; Chiba, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Arai
authors.affiliation: Institute of Medical Science; University of Tokyo; Minato-ku, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kurahashi
authors.affiliation: Cellular Informatics Laboratory; RIKEN Advanced Science Institute; Wako-shi, Saitama, Japan.
authors.forename: Chan-Gi
authors.initials: CG
authors.lastname: Pack
authors.affiliation: Cellular Informatics Laboratory; RIKEN Advanced Science Institute; Wako-shi, Saitama, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sako
authors.affiliation: Institute of Medical Science; University of Tokyo; Minato-ku, Tokyo, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Nakamura
keywords: GET pathway; HSR; Hsp104; Sgt2; Ssa1; [PSI+]; eRF-3; misfolded multi-trans membranes; prion clearance; yeast prion
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