{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Xu S"],"funding":["CSC | Chinese Government Scholarship","Vetenskapsrådet","EU Joint Programme – Neurodegenerative Disease Research","Deutsche Forschungsgemeinschaft","Deutsche Forschungsgemeinschaft (German Research Foundation)","Cancerfonden (Swedish Cancer Society)","Vetenskapsrådet (Swedish Research Council)","EU Joint Programme - Neurodegenerative Disease Research (Programi i Përbashkët i BE-së për Kërkimet mbi Sëmundjet Neuro-degjeneruese)","Cancerfonden"],"pagination":["1282"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11461528"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7(1)"],"pubmed_abstract":["Inhibitors of the integrated stress response (ISR) have been used to explore the potential beneficial effects of reducing the activation of this pathway in diseases. As the ISR is in essence a protective response, there is, however, a risk that inhibition may compromise the cell's ability to restore protein homeostasis. Here, we show that the experimental compound ISRIB impairs degradation of proteins by the ubiquitin-proteasome system (UPS) during proteotoxic stress in the cytosolic, but not nuclear, compartment. Accumulation of a UPS reporter substrate that is intercepted by ribosome quality control was comparable to the level observed after blocking the UPS with a proteasome inhibitor. Consistent with impairment of the cytosolic UPS, ISRIB treatment caused an accumulation of polyubiquit"],"journal":["Communications biology"],"pubmed_title":["Chemical inhibition of the integrated stress response impairs the ubiquitin-proteasome system."],"pmcid":["PMC11461528"],"funding_grant_id":["2021-02562, 2015-06794","PP-829-050","GI-1329/1-1","CAN211653Pj"],"pubmed_authors":["Barchi E","Alberti S","Xu S","Poser I","Gierisch ME","Dantuma NP","Salomons FA"],"additional_accession":[]},"is_claimable":false,"name":"Chemical inhibition of the integrated stress response impairs the ubiquitin-proteasome system.","description":"Inhibitors of the integrated stress response (ISR) have been used to explore the potential beneficial effects of reducing the activation of this pathway in diseases. As the ISR is in essence a protective response, there is, however, a risk that inhibition may compromise the cell's ability to restore protein homeostasis. Here, we show that the experimental compound ISRIB impairs degradation of proteins by the ubiquitin-proteasome system (UPS) during proteotoxic stress in the cytosolic, but not nuclear, compartment. Accumulation of a UPS reporter substrate that is intercepted by ribosome quality control was comparable to the level observed after blocking the UPS with a proteasome inhibitor. Consistent with impairment of the cytosolic UPS, ISRIB treatment caused an accumulation of polyubiquit","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Oct","modification":"2026-07-14T20:40:52.599Z","creation":"2025-04-04T19:45:28.527Z"},"accession":"S-EPMC11461528","cross_references":{"pubmed":["39379572"],"doi":["10.1038/s42003-024-06974-0"]}}