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

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 ou...

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Autores principales: Bhattacharya, Kaushik, Weidenauer, Lorenz, Luengo, Tania Morán, Pieters, Ellis C., Echeverría, Pablo C., Bernasconi, Lilia, Wider, Diana, Sadian, Yashar, Koopman, Margreet B., Villemin, Matthieu, Bauer, Christoph, Rüdiger, Stefan G. D., Quadroni, Manfredo, Picard, Didier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688965/
https://www.ncbi.nlm.nih.gov/pubmed/33239621
http://dx.doi.org/10.1038/s41467-020-19783-w
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author Bhattacharya, Kaushik
Weidenauer, Lorenz
Luengo, Tania Morán
Pieters, Ellis C.
Echeverría, Pablo C.
Bernasconi, Lilia
Wider, Diana
Sadian, Yashar
Koopman, Margreet B.
Villemin, Matthieu
Bauer, Christoph
Rüdiger, Stefan G. D.
Quadroni, Manfredo
Picard, Didier
author_facet Bhattacharya, Kaushik
Weidenauer, Lorenz
Luengo, Tania Morán
Pieters, Ellis C.
Echeverría, Pablo C.
Bernasconi, Lilia
Wider, Diana
Sadian, Yashar
Koopman, Margreet B.
Villemin, Matthieu
Bauer, Christoph
Rüdiger, Stefan G. D.
Quadroni, Manfredo
Picard, Didier
author_sort Bhattacharya, Kaushik
collection PubMed
description 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 proteasome 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, compensates 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.
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spelling pubmed-76889652020-12-03 The Hsp70-Hsp90 co-chaperone Hop/Stip1 shifts the proteostatic balance from folding towards degradation Bhattacharya, Kaushik Weidenauer, Lorenz Luengo, Tania Morán Pieters, Ellis C. Echeverría, Pablo C. Bernasconi, Lilia Wider, Diana Sadian, Yashar Koopman, Margreet B. Villemin, Matthieu Bauer, Christoph Rüdiger, Stefan G. D. Quadroni, Manfredo Picard, Didier Nat Commun Article 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 proteasome 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, compensates 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. Nature Publishing Group UK 2020-11-25 /pmc/articles/PMC7688965/ /pubmed/33239621 http://dx.doi.org/10.1038/s41467-020-19783-w Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Bhattacharya, Kaushik
Weidenauer, Lorenz
Luengo, Tania Morán
Pieters, Ellis C.
Echeverría, Pablo C.
Bernasconi, Lilia
Wider, Diana
Sadian, Yashar
Koopman, Margreet B.
Villemin, Matthieu
Bauer, Christoph
Rüdiger, Stefan G. D.
Quadroni, Manfredo
Picard, Didier
The Hsp70-Hsp90 co-chaperone Hop/Stip1 shifts the proteostatic balance from folding towards degradation
title The Hsp70-Hsp90 co-chaperone Hop/Stip1 shifts the proteostatic balance from folding towards degradation
title_full The Hsp70-Hsp90 co-chaperone Hop/Stip1 shifts the proteostatic balance from folding towards degradation
title_fullStr The Hsp70-Hsp90 co-chaperone Hop/Stip1 shifts the proteostatic balance from folding towards degradation
title_full_unstemmed The Hsp70-Hsp90 co-chaperone Hop/Stip1 shifts the proteostatic balance from folding towards degradation
title_short The Hsp70-Hsp90 co-chaperone Hop/Stip1 shifts the proteostatic balance from folding towards degradation
title_sort hsp70-hsp90 co-chaperone hop/stip1 shifts the proteostatic balance from folding towards degradation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688965/
https://www.ncbi.nlm.nih.gov/pubmed/33239621
http://dx.doi.org/10.1038/s41467-020-19783-w
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