Dataset Information

The Hsp70/hsp90 Co-chaperone Hop/stip1 Shifts the Proteostatic Balance From Folding Towards Degradation

ABSTRACT: 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. Similarly to budding yeast (ref), human cell lines 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 an alternate proteostatic equilibrium. Thus, Hop may be actionable for cells to shift the proteostatic balance between folding and degradation.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

SUBMITTER: Manfredo Quadroni

LAB HEAD: Didier Picard

PROVIDER: PXD012774 | Pride | 2020-11-09

REPOSITORIES: Pride

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			Action	DRS
	171218_Kaushik_9997-OT-1.raw	Raw
	171218_Kaushik_9997-OT-2.raw	Raw
	171218_Kaushik_9998-OT-1.raw	Raw
	171218_Kaushik_9998-OT-2.raw	Raw
	180120_Kaushik_10087-OT-2.raw	Raw

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

Bhattacharya Kaushik K Weidenauer Lorenz L Luengo Tania Morán TM Pieters Ellis C EC Echeverría Pablo C PC Bernasconi Lilia L Wider Diana D Sadian Yashar Y Koopman Margreet B MB Villemin Matthieu M Bauer Christoph C Rüdiger Stefan G D SGD Quadroni Manfredo M Picard Didier D

Nature communications 20201125 1

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 cap ...[more]

PMID: 33239621

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