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

Research output: Contribution to journalResearch articleContributedpeer-review


  • Shanshan Xu - , Karolinska Institutet (Author)
  • Maria E. Gierisch - , Karolinska Institutet (Author)
  • Anna Katharina Schellhaus - , Karolinska Institutet (Author)
  • Ina Poser - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Simon Alberti - , Chair of Cellular Biochemistry (Author)
  • Florian A. Salomons - , Karolinska Institutet (Author)
  • Nico P. Dantuma - , Karolinska Institutet (Author)


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.


Original languageEnglish
Article numbere111802
Number of pages19
JournalEMBO Journal
Volume42 (2023)
Issue number3
Publication statusPublished - 27 Dec 2022

External IDs

PubMed 36574355
ORCID /0000-0003-4017-6505/work/147143312



  • SUMO, protein quality control, proteostasis, stress granules, ubiquitin-proteasome system, Proteasome Endopeptidase Complex/metabolism, Transcription Factors/metabolism, Stress Granules, Ubiquitin/metabolism, Nuclear Proteins/genetics

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