{"doi":"10.1016/j.celrep.2016.05.032","title":"CYLD Proteolysis Protects Macrophages from TNF-Mediated Auto-necroptosis Induced by LPS and Licensed by Type I IFN","abstract":null,"journal":"Cell Reports","year":2016,"id":665272,"datarank":0.6995158641168101,"base_score":4.663439094112067,"endowment":4.663439094112067,"self_citation_contribution":0.6995158641168101,"citation_network_contribution":0.0,"self_endowment_contribution":0.6995158641168101,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":105,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1737203,"name":"Scott J. Justus","orcid":null,"position":1,"is_corresponding":false},{"id":1737205,"name":"Rosalind L. Ang","orcid":null,"position":2,"is_corresponding":false},{"id":1737208,"name":"Nimisha Rikhi","orcid":null,"position":3,"is_corresponding":false},{"id":373654,"name":"Wenjing Li","orcid":"0000-0003-1154-2895","position":4,"is_corresponding":false},{"id":1737211,"name":"Thomas M. Moran","orcid":null,"position":5,"is_corresponding":false},{"id":1737212,"name":"Jianke Zhang","orcid":null,"position":6,"is_corresponding":false},{"id":608819,"name":"Emiko Mizoguchi","orcid":"0000-0002-4019-0617","position":7,"is_corresponding":false},{"id":631164,"name":"Matija Zelic","orcid":null,"position":8,"is_corresponding":false},{"id":1662049,"name":"Michelle A. Kelliher","orcid":null,"position":9,"is_corresponding":false},{"id":1737213,"name":"J. Magarian Blander","orcid":null,"position":10,"is_corresponding":false},{"id":1737214,"name":"Adrian T. Ting","orcid":null,"position":11,"is_corresponding":false},{"id":490521,"name":"Diana Legarda","orcid":"0000-0003-3177-129X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"CYLD Proteolysis Protects Macrophages from TNF-Mediated Auto-necroptosis Induced by LPS and Licensed by Type I IFN","abstract":"Tumor necrosis factor (TNF) induces necroptosis, a RIPK3/MLKL-dependent form of inflammatory cell death. In response to infection by Gram-negative bacteria, multiple receptors on macrophages, including TLR4, TNF, and type I IFN receptors, are concurrently activated, but it is unclear how they crosstalk to regulate necroptosis. We report that TLR4 activates CASPASE-8 to cleave and remove the deubiquitinase cylindromatosis (CYLD) in a TRIF- and RIPK1-dependent manner to disable necroptosis in macrophages. Inhibiting CASPASE-8 leads to CYLD-dependent necroptosis caused by the TNF produced in response to TLR4 ligation. While lipopolysaccharides (LPS)-induced necroptosis was abrogated in Tnf(-/-) macrophages, a soluble TNF antagonist was not able to do so in Tnf(+/+) macrophages, indicating that necroptosis occurs in a cell-autonomous manner. Surprisingly, TNF-mediated auto-necroptosis of macrophages requires type I IFN, which primes the expression of key necroptosis-signaling molecules, including TNFR2 and MLKL. Thus, the TNF necroptosis pathway is regulated by both negative and positive crosstalk.","is_dataset_classified":null,"base_score":4.663439094112067,"endowment":4.663439094112067,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"27264187","pmcid":"PMC4909532","openalex_id":"https://openalex.org/W2418951526","authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI081807","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"T32 AI078892","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"HHSN272201000054C","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI095245","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK080070","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R56 AI075118","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"P01 DK072201","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 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Cells"}],"total_grants":19,"fwci":5.0766,"citation_percentile":0.95962672,"influential_citations":0,"citation_trend":[{"year":2016,"count":5},{"year":2017,"count":12},{"year":2018,"count":11},{"year":2019,"count":8},{"year":2020,"count":14},{"year":2021,"count":9},{"year":2022,"count":8},{"year":2023,"count":11},{"year":2024,"count":14},{"year":2025,"count":6},{"year":2026,"count":7}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"http://www.cell.com/article/S2211124716306155/pdf","host_type":"journal"},{"url":"http://www.cell.com/article/S2211124716306155/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S2211124716306155?httpAccept=text/plain","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S2211124716306155?httpAccept=text/xml","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.celrep.2016.05.032","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/27264187","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4909532","host_type":"repository"},{"url":"https://escholarship.umassmed.edu/oapubs/2807","host_type":"repository"},{"url":"https://doaj.org/article/8c0a3848a6e94f09b0ce11ed75eae8fa","host_type":"repository"},{"url":"http://dx.doi.org/10.1016/j.celrep.2016.05.032","host_type":""},{"url":"https://dx.doi.org/10.1016/j.celrep.2016.05.032","host_type":""},{"url":"https://doi.org/https://doi.org/20.500.14038/39998","host_type":""},{"url":"https://doi.org/https://doi.org/10.1016/j.celrep.2016.05.032","host_type":""}],"fields_of_study":["Immune Response and Inflammation","Cell death mechanisms and regulation","Inflammasome and immune disorders","0301 basic medicine","03 medical and health sciences","0303 health sciences","Adaptor Proteins, Vesicular Transport","Animals","Apoptosis","Caspase 8","Cysteine Endopeptidases","Cytoprotection","Deubiquitinating Enzyme CYLD","Interferon Type I","Lipopolysaccharides","Macrophages","Mice","Mice, Inbred C57BL","Mice, Transgenic","Models, Biological","Necrosis","Protein Kinases","Proteolysis","Receptors, Tumor Necrosis Factor, Type II","Signal Transduction","Toll-Like Receptor 4","Tumor Necrosis Factor-alpha"],"mesh_terms":["Deubiquitinating Enzyme CYLD","Animals","Cysteine Endopeptidases","Interferon Type I","Lipopolysaccharides","Macrophages","Mice, Inbred C57BL","Mice, Transgenic","Models, Biological","Necrosis","Protein Kinases","Tumor Necrosis Factor-alpha","Signal Transduction","Apoptosis","Cytoprotection","Adaptor Proteins, Vesicular Transport","Receptors, Tumor Necrosis Factor, Type II","Toll-Like Receptor 4","Mice","Caspase 8","Proteolysis"],"keywords":["Necroptosis","TRIF","RIPK1","Cell biology","Tumor necrosis factor alpha","TLR4","Biology","Crosstalk","Cytokine","Programmed cell death","Signal transduction","Receptor","Apoptosis","Immunology","Innate immune system","Toll-like receptor","Biochemistry","Lipopolysaccharides","QH301-705.5","Mice, Transgenic","Models, Biological","Mice","Necrosis","Animals","Receptors, Tumor Necrosis Factor, Type II","Biology (General)","Cancer Biology","Caspase 8","Macrophages","Deubiquitinating Enzyme CYLD","Mice, Inbred C57BL","Toll-Like Receptor 4","Adaptor Proteins, Vesicular Transport","Cysteine Endopeptidases","Cytoprotection","Interferon Type I","Proteolysis","Protein Kinases"],"sdg_mappings":[{"sdg_number":2,"sdg_label":"2. 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