The Hsp70-Hsp90 co-chaperone Hop/Stip1 shifts the proteostatic balance from folding towards degradation

Article Article scientifique Article The Hsp70-Hsp90 co-chaperone Hop/Stip1 shifts the proteostatic balance from folding towards degradation eng 2020 author Bhattacharya Kaushik 829415 author Weidenauer Lorenz author Luengo Tania Morán author Pieters Ellis C. author Echeverria Pablo 665334 Pablo Christian Echeverria author Bernasconi Lilia 66998 author Wider Diana 133829 author Sadian Yashar 917818 author Koopman Margreet B. author Villemin Matthieu 873408 author Bauer Christoph Ruediger 134757 author Rüdiger Stefan G. D. author Quadroni Manfredo author Picard Didier 0000-0001-8816-9668 26830 10.1038/s41467-020-19783-w 2041-1723 http://www.nature.com/articles/s41467-020-19783-w Hop/Stip1/Sti1 is thought to be essential as a co-chaperone to facilitate substrate transfer between the Hsp70 and Hsp90 molecular chaperones. Despite this proposed key function for protein folding and maturation, it is not essential in a number of eukaryotes and bacteria lack an ortholog. We set out to identify and to characterize its eukaryote-specific function. Human cell lines and the budding yeast with deletions of the Hop/Sti1 gene display reduced pro- teasome activity due to inefficient capping of the core particle with regulatory particles. Unexpectedly, knock-out cells are more proficient at preventing protein aggregation and at promoting protein refolding. Without the restraint by Hop, a more efficient folding activity of the prokaryote-like Hsp70-Hsp90 complex, which can also be demonstrated in vitro, com- pensates for the proteasomal defect and ensures the proteostatic equilibrium. Thus, cells may act on the level and/or activity of Hop to shift the proteostatic balance between folding and degradation. Dewey 570 Dewey 590 44 Département de génétique et évolution 162 46 Département de biologie cellulaire 165 false 838 Groupe Picard Nature Communications 11 5975 bf41f31a-46ca-4f09-a73d-5781b87fef28 Article (Published version) Public s41467-020-19783-w.pdf 13595265 application/pdf openAccess Faculté des sciences / Section de biologie / Département de génétique et évolution Faculté des sciences / Section de biologie / Département de biologie cellulaire

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The Hsp70-Hsp90 co-chaperone Hop/Stip1 shifts the proteostatic balance from folding towards degradation	Nature Communications			2020	310	253

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