The extent of Ssa1/Ssa2 Hsp70 chaperone involvement in nuclear protein quality control degradation varies with the substrate.

Autor:	Jones RD; Department of Pharmacology, University of Washington, Seattle, WA 98195., Enam C; Department of Pharmacology, University of Washington, Seattle, WA 98195., Ibarra R; Department of Chemistry and Biochemistry, University of Nevada, Las Vegas, NV 89154., Borror HR; Department of Pharmacology, University of Washington, Seattle, WA 98195., Mostoller KE; Department of Pharmacology, University of Washington, Seattle, WA 98195., Fredrickson EK; Department of Pharmacology, University of Washington, Seattle, WA 98195., Lin J; Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104., Chuang E; Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104., March Z; Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104., Shorter J; Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104., Ravid T; Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Givat-Ram, -Jerusalem 91904, Israel., Kleiger G; Department of Chemistry and Biochemistry, University of Nevada, Las Vegas, NV 89154., Gardner RG; Department of Pharmacology, University of Washington, Seattle, WA 98195.
Jazyk:	angličtina
Zdroj:	Molecular biology of the cell [Mol Biol Cell] 2020 Feb 01; Vol. 31 (3), pp. 221-233. Date of Electronic Publication: 2019 Dec 11.
DOI:	10.1091/mbc.E18-02-0121
Abstrakt:	Protein misfolding is a recurring phenomenon that cells must manage; otherwise misfolded proteins can aggregate and become toxic should they persist. To counter this burden, cells have evolved protein quality control (PQC) mechanisms that manage misfolded proteins. Two classes of systems that function in PQC are chaperones that aid in protein folding and ubiquitin-protein ligases that ubiquitinate misfolded proteins for proteasomal degradation. How folding and degradative PQC systems interact and coordinate their respective functions is not yet fully understood. Previous studies of PQC degradation pathways in the endoplasmic reticulum and cytosol have led to the prevailing idea that these pathways require the activity of Hsp70 chaperones. Here, we find that involvement of the budding yeast Hsp70 chaperones Ssa1 and Ssa2 in nuclear PQC degradation varies with the substrate. In particular, nuclear PQC degradation mediated by the yeast ubiquitin-protein ligase San1 often involves Ssa1/Ssa2, but San1 substrate recognition and ubiquitination can proceed without these Hsp70 chaperone functions in vivo and in vitro. Our studies provide new insights into the variability of Hsp70 chaperone involvement with a nuclear PQC degradation pathway.
Databáze:	MEDLINE
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