{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Panganiban RA"],"funding":["HHS | NIH | National Institute of Environmental Health Sciences","NIEHS NIH HHS","NHLBI NIH HHS"],"pagination":["13384-13393"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6613086"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["116(27)"],"pubmed_abstract":["Sensing misfolded proteins in the endoplasmic reticulum (ER), cells initiate the ER stress response and, when overwhelmed, undergo apoptosis. However, little is known about how cells prevent excessive ER stress response and cell death to restore homeostasis. Here, we report the identification and characterization of cellular suppressors of ER stress-induced apoptosis. Using a genome-wide CRISPR library, we screen for genes whose inactivation further increases ER stress-induced up-regulation of C/EBP homologous protein 10 (CHOP)-the transcription factor central to ER stress-associated apoptosis. Among the top validated hits are two interacting components of the polycomb repressive complex (<i>L3MBTL2</i> [L(3)Mbt-Like 2] and <i>MGA</i> [MAX gene associated]), and microRNA-124-3 (miR-124-3). CRISPR knockout of these genes increases CHOP expression and sensitizes cells to apoptosis induced by multiple ER stressors, while overexpression confers the opposite effects. L3MBTL2 associates with the <i>CHOP</i> promoter in unstressed cells to repress CHOP induction but dissociates from the promoter in the presence of ER stress, whereas miR-124-3 directly targets the IRE1 branch of the ER stress pathway. Our study reveals distinct mechanisms that suppress ER stress-induced apoptosis and may lead to a better understanding of diseases whose pathogenesis is linked to overactive ER stress response."],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Genome-wide CRISPR screen identifies suppressors of endoplasmic reticulum stress-induced apoptosis."],"pmcid":["PMC6613086"],"funding_grant_id":["P30 ES000002","R01 HL133433","P30ES000002","R)1ES029097","K99 ES029548","R01ES02230","R01 ES029097"],"pubmed_authors":["Park HR","Sun M","Panganiban RA","Shumyatcher M","Himes BE","Lu Q"],"additional_accession":[]},"is_claimable":false,"name":"Genome-wide CRISPR screen identifies suppressors of endoplasmic reticulum stress-induced apoptosis.","description":"Sensing misfolded proteins in the endoplasmic reticulum (ER), cells initiate the ER stress response and, when overwhelmed, undergo apoptosis. However, little is known about how cells prevent excessive ER stress response and cell death to restore homeostasis. Here, we report the identification and characterization of cellular suppressors of ER stress-induced apoptosis. Using a genome-wide CRISPR library, we screen for genes whose inactivation further increases ER stress-induced up-regulation of C/EBP homologous protein 10 (CHOP)-the transcription factor central to ER stress-associated apoptosis. Among the top validated hits are two interacting components of the polycomb repressive complex (<i>L3MBTL2</i> [L(3)Mbt-Like 2] and <i>MGA</i> [MAX gene associated]), and microRNA-124-3 (miR-124-3). CRISPR knockout of these genes increases CHOP expression and sensitizes cells to apoptosis induced by multiple ER stressors, while overexpression confers the opposite effects. L3MBTL2 associates with the <i>CHOP</i> promoter in unstressed cells to repress CHOP induction but dissociates from the promoter in the presence of ER stress, whereas miR-124-3 directly targets the IRE1 branch of the ER stress pathway. Our study reveals distinct mechanisms that suppress ER stress-induced apoptosis and may lead to a better understanding of diseases whose pathogenesis is linked to overactive ER stress response.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Jul","modification":"2025-04-05T16:21:21.809Z","creation":"2025-04-05T16:21:21.809Z"},"accession":"S-EPMC6613086","cross_references":{"pubmed":["31213543"],"doi":["10.1073/pnas.1906275116"]}}