Cytosolic stress granules relieve the ubiquitin-proteasome system in the nuclear compartment.
SUMO
protein quality control
proteostasis
stress granules
ubiquitin-proteasome system
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
01 02 2023
01 02 2023
Historique:
revised:
25
11
2022
received:
01
06
2022
accepted:
01
12
2022
pubmed:
28
12
2022
medline:
3
2
2023
entrez:
27
12
2022
Statut:
ppublish
Résumé
The role of cytosolic stress granules in the integrated stress response has remained largely enigmatic. Here, we studied the functionality of the ubiquitin-proteasome system (UPS) in cells that were unable to form stress granules. Surprisingly, the inability of cells to form cytosolic stress granules had primarily a negative impact on the functionality of the nuclear UPS. While defective ribosome products (DRiPs) accumulated at stress granules in thermally stressed control cells, they localized to nucleoli in stress granule-deficient cells. The nuclear localization of DRiPs was accompanied by redistribution and enhanced degradation of SUMOylated proteins. Depletion of the SUMO-targeted ubiquitin ligase RNF4, which targets SUMOylated misfolded proteins for proteasomal degradation, largely restored the functionality of the UPS in the nuclear compartment in stress granule-deficient cells. Stress granule-deficient cells showed an increase in the formation of mutant ataxin-1 nuclear inclusions when exposed to thermal stress. Our data reveal that stress granules play an important role in the sequestration of cytosolic misfolded proteins, thereby preventing these proteins from accumulating in the nucleus, where they would otherwise infringe nuclear proteostasis.
Identifiants
pubmed: 36574355
doi: 10.15252/embj.2022111802
pmc: PMC9890234
doi:
Substances chimiques
Proteasome Endopeptidase Complex
EC 3.4.25.1
Ubiquitin
0
Nuclear Proteins
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e111802Informations de copyright
© 2022 The Authors. Published under the terms of the CC BY 4.0 license.
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