Cytosolic stress granules relieve the ubiquitin‐proteasome system in the nuclear compartment

Abstract: 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.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
Cytosolic stress granules relieve the ubiquitin‐proteasome system in the nuclear compartment ; day:27 ; month:12 ; year:2022 ; extent:19
The EMBO journal / European Molecular Biology Organization ; (27.12.2022) (gesamt 19)

Urheber
Xu, Shanshan
Gierisch, Maria E.
Schellhaus, Anna Katharina
Poser, Ina
Alberti, Simon Marc
Salomons, Florian A.
Dantuma, Nico P.

DOI
10.15252/embj.2022111802
URN
urn:nbn:de:101:1-2022122814011174081260
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:22 MESZ

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Beteiligte

  • Xu, Shanshan
  • Gierisch, Maria E.
  • Schellhaus, Anna Katharina
  • Poser, Ina
  • Alberti, Simon Marc
  • Salomons, Florian A.
  • Dantuma, Nico P.

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