{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["22(11)"],"submitter":["Petersen SL"],"pubmed_abstract":["Tumor necrosis factor α (TNFα) triggers necroptotic cell death through an intracellular signaling complex containing receptor-interacting protein kinase (RIPK) 1 and RIPK3, called the necrosome. RIPK1 phosphorylates RIPK3, which phosphorylates the pseudokinase mixed lineage kinase-domain-like (MLKL)-driving its oligomerization and membrane-disrupting necroptotic activity. Here, we show that TNF receptor-associated factor 2 (TRAF2)-previously implicated in apoptosis suppression-also inhibits necroptotic signaling by TNFα. TRAF2 disruption in mouse fibroblasts augmented TNFα-driven necrosome formation and RIPK3-MLKL association, promoting necroptosis. TRAF2 constitutively associated with MLKL, whereas TNFα reversed this via cylindromatosis-dependent TRAF2 deubiquitination. Ectopic interactio"],"journal":["Cell death and differentiation"],"pagination":["1846-57"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4648330"],"repository":["biostudies-literature"],"pubmed_title":["TRAF2 is a biologically important necroptosis suppressor."],"pmcid":["PMC4648330"],"pubmed_authors":["Gonzalvez F","Marsters SA","Petersen SL","Ashkenazi A","Lawrence DA","Chen TT"],"additional_accession":[]},"is_claimable":false,"name":"TRAF2 is a biologically important necroptosis suppressor.","description":"Tumor necrosis factor α (TNFα) triggers necroptotic cell death through an intracellular signaling complex containing receptor-interacting protein kinase (RIPK) 1 and RIPK3, called the necrosome. RIPK1 phosphorylates RIPK3, which phosphorylates the pseudokinase mixed lineage kinase-domain-like (MLKL)-driving its oligomerization and membrane-disrupting necroptotic activity. Here, we show that TNF receptor-associated factor 2 (TRAF2)-previously implicated in apoptosis suppression-also inhibits necroptotic signaling by TNFα. TRAF2 disruption in mouse fibroblasts augmented TNFα-driven necrosome formation and RIPK3-MLKL association, promoting necroptosis. TRAF2 constitutively associated with MLKL, whereas TNFα reversed this via cylindromatosis-dependent TRAF2 deubiquitination. Ectopic interactio","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015 Nov","modification":"2025-04-22T15:14:23.331Z","creation":"2019-03-27T02:02:07Z"},"accession":"S-EPMC4648330","cross_references":{"pubmed":["25882049"],"doi":["10.1038/cdd.2015.35"]}}