{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["A Avelar R"],"funding":["U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)","NIDDK NIH HHS","U.S. Department of Health & Human Services | NIH | National Cancer Institute","U.S. Department of Defense","U-M | Horace H. Rackham School of Graduate Studies, University of Michigan (Rackham Graduate School)","U.S. Department of Defense (United States Department of Defense)","NCI NIH HHS","NIGMS NIH HHS","U-M | Horace H. Rackham School of Graduate Studies, University of Michigan"],"pagination":["1761-1775"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11618521"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["31(12)"],"pubmed_abstract":["The integrated stress response (ISR) regulates cell fate during conditions of stress by leveraging the cell's capacity to endure sustainable and efficient adaptive stress responses. Protein phosphatase 2A (PP2A) activity modulation has been shown to be successful in achieving both therapeutic efficacy and safety across various cancer models. However, the molecular mechanisms driving its selective antitumor effects remain unclear. Here, we show for the first time that ISR plasticity relies on PP2A activation to regulate drug response and dictate cellular survival under conditions of chronic stress. We demonstrate that genetic and chemical modulation of the PP2A leads to chronic proteolytic stress and triggers an ISR to dictate whether the cell lives or dies. More specifically, we uncovered "],"journal":["Cell death and differentiation"],"pubmed_title":["Integrated stress response plasticity governs normal cell adaptation to chronic stress via the PP2A-TFE3-ATF4 pathway."],"pmcid":["PMC11618521"],"funding_grant_id":["OC210149","N/A","R01 DK132017","R01 GM094231","P30 CA046592","R01 CA197780","R01 DK048280","R01CA197780"],"pubmed_authors":["Gupta R","Jasti M","O'Connor CM","Shenolikar S","A Avelar R","Arvan P","Colina J","DiFeo A","da Veiga Leprevost F","Carvette G","Teitel J","Hatzoglou M","Nesvizhskii AI","Narla G"],"additional_accession":[]},"is_claimable":false,"name":"Integrated stress response plasticity governs normal cell adaptation to chronic stress via the PP2A-TFE3-ATF4 pathway.","description":"The integrated stress response (ISR) regulates cell fate during conditions of stress by leveraging the cell's capacity to endure sustainable and efficient adaptive stress responses. Protein phosphatase 2A (PP2A) activity modulation has been shown to be successful in achieving both therapeutic efficacy and safety across various cancer models. However, the molecular mechanisms driving its selective antitumor effects remain unclear. Here, we show for the first time that ISR plasticity relies on PP2A activation to regulate drug response and dictate cellular survival under conditions of chronic stress. We demonstrate that genetic and chemical modulation of the PP2A leads to chronic proteolytic stress and triggers an ISR to dictate whether the cell lives or dies. More specifically, we uncovered ","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Dec","modification":"2026-06-02T03:37:23.655Z","creation":"2025-04-04T01:58:06.621Z"},"accession":"S-EPMC11618521","cross_references":{"pubmed":["39349971"],"doi":["10.1038/s41418-024-01378-3"]}}