{"doi":"10.7554/elife.52241","title":"PACT-mediated PKR activation acts as a hyperosmotic stress intensity sensor weakening osmoadaptation and enhancing inflammation","abstract":"The inability of cells to adapt to increased environmental tonicity can lead to inflammatory gene expression and pathogenesis. The Rel family of transcription factors TonEBP and NF-κB p65 play critical roles in the switch from osmoadaptive homeostasis to inflammation, respectively. Here we identified PACT-mediated PKR kinase activation as a marker of the termination of adaptation and initiation of inflammation in Mus musculus embryonic fibroblasts. We found that high stress-induced PACT-PKR activation inhibits the interaction between NF-κB c-Rel and TonEBP essential for the increased expression of TonEBP-dependent osmoprotective genes. This resulted in enhanced formation of TonEBP/NF-κB p65 complexes and enhanced proinflammatory gene expression. These data demonstrate a novel role of c-Rel in the adaptive response to hyperosmotic stress, which is inhibited via a PACT/PKR-dependent dimer redistribution of the Rel family transcription factors. Our results suggest that inhibiting PACT-PKR signaling may prove a novel target for alleviating stress-induced inflammatory diseases.","journal":"eLife","year":2020,"id":96376,"datarank":1.173924223684816,"base_score":3.5553480614894135,"endowment":3.5553480614894135,"self_citation_contribution":0.5333022092234121,"citation_network_contribution":0.6406220144614039,"self_endowment_contribution":0.5333022092234121,"citer_contribution":0.6406220144614039,"corpus_percentile":null,"corpus_rank":null,"citation_count":34,"citer_count":29,"citers_with_citation_signal":24,"citers_with_endowment":24,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE138692"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":457850,"name":"Dawid Krokowski","orcid":null,"position":1,"is_corresponding":false},{"id":429273,"name":"Bo‐Jhih Guan","orcid":null,"position":2,"is_corresponding":false},{"id":456389,"name":"Zhaofeng Gao","orcid":"0000-0002-6960-465X","position":3,"is_corresponding":false},{"id":456387,"name":"Xing‐Huang Gao","orcid":"0000-0002-0720-3690","position":4,"is_corresponding":false},{"id":477645,"name":"Jing Wu","orcid":"0000-0001-8838-8692","position":5,"is_corresponding":false},{"id":478323,"name":"Raul Jobava","orcid":null,"position":6,"is_corresponding":false},{"id":398884,"name":"Greeshma Ray","orcid":null,"position":7,"is_corresponding":false},{"id":327818,"name":"Tristan J de Jesus","orcid":null,"position":8,"is_corresponding":false},{"id":254430,"name":"Massimiliano G. Bianchi","orcid":"0000-0002-4179-6573","position":9,"is_corresponding":false},{"id":477646,"name":"Evelyn Chukwurah","orcid":"0000-0002-9706-7003","position":10,"is_corresponding":false},{"id":254432,"name":"Ovidio Bussolati","orcid":"0000-0002-4301-2939","position":11,"is_corresponding":false},{"id":254431,"name":"Michael S. Kilberg","orcid":"0000-0002-6009-3822","position":12,"is_corresponding":false},{"id":428228,"name":"David A. Buchner","orcid":"0000-0003-3920-4871","position":13,"is_corresponding":false},{"id":240328,"name":"Ganes C. Sen","orcid":"0000-0002-9692-0631","position":14,"is_corresponding":false},{"id":478324,"name":"Calvin U. Cotton","orcid":null,"position":15,"is_corresponding":false},{"id":302610,"name":"Christine McDonald","orcid":"0000-0002-6745-9487","position":16,"is_corresponding":false},{"id":398001,"name":"Michelle S. Longworth","orcid":"0000-0002-1313-1777","position":17,"is_corresponding":false},{"id":326799,"name":"Parameswaran Ramakrishnan","orcid":"0000-0002-1314-827X","position":18,"is_corresponding":false},{"id":428227,"name":"Maria Hatzoglou","orcid":"0000-0003-2037-1231","position":19,"is_corresponding":false},{"id":477644,"name":"Kenneth T. Farabaugh","orcid":"0000-0002-9591-0466","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":null,"created_at":"2026-07-18T22:34:34.781847Z","pmid":"32175843","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}