Non-enzymatic cleavage of Hsp90 by oxidative stress leads to actin aggregate formation: A novel gain-of-function mechanism.
Heat shock protein 90
Oxidative stress
Proteasome
Protein aggregates
Protein oxidation
Journal
Redox biology
ISSN: 2213-2317
Titre abrégé: Redox Biol
Pays: Netherlands
ID NLM: 101605639
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
16
12
2018
revised:
04
01
2019
accepted:
10
01
2019
pubmed:
21
1
2019
medline:
2
4
2019
entrez:
21
1
2019
Statut:
ppublish
Résumé
Aging is accompanied by the accumulation of oxidized proteins. To remove them, cells employ the proteasomal and autophagy-lysosomal systems; however, if the clearance rate is inferior to its formation, protein aggregates form as a hallmark of proteostasis loss. In cells, during stress conditions, actin aggregates accumulate leading to impaired proliferation and reduced proteasomal activity, as observed in cellular senescence. The heat shock protein 90 (Hsp90) is a molecular chaperone that binds and protects the proteasome from oxidative inactivation. We hypothesized that in oxidative stress conditions a malfunction of Hsp90 occurs resulting in the aforementioned protein aggregates. Here, we demonstrate that upon oxidative stress Hsp90 loses its function in a highly specific non-enzymatic iron-catalyzed oxidation event and its breakdown product, a cleaved form of Hsp90 (Hsp90cl), acquires a new function in mediating the accumulation of actin aggregates. Moreover, the prevention of Hsp90 cleavage reduces oxidized actin accumulation, whereas transfection of the cleaved form of Hsp90 leads to an enhanced accumulation of oxidized actin. This indicates a clear role of the Hsp90cl in the aggregation of oxidized proteins.
Identifiants
pubmed: 30660959
pii: S2213-2317(18)31236-9
doi: 10.1016/j.redox.2019.101108
pmc: PMC6348241
pii:
doi:
Substances chimiques
Actins
0
HSP90 Heat-Shock Proteins
0
Protein Aggregates
0
Iron
E1UOL152H7
Proteasome Endopeptidase Complex
EC 3.4.25.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
101108Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.
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