{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Rodriguez DA"],"funding":["Deutsche Forschungsgemeinschaft","NIAID NIH HHS","HHS | NIH | National Cancer Institute","Foundation for the National Institutes of Health","NCI NIH HHS","U.S National Cancer Institute"],"pagination":["e2207240119"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9565532"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["119(41)"],"pubmed_abstract":["The absence of Caspase-8 or its adapter, Fas-associated death domain (FADD), results in activation of receptor interacting protein kinase-3 (RIPK3)- and mixed-lineage kinase-like (MLKL)-dependent necroptosis in vivo. Here, we show that spontaneous activation of RIPK3, phosphorylation of MLKL, and necroptosis in Caspase-8- or FADD-deficient cells was dependent on the nucleic acid sensor, Z-DNA binding protein-1 (ZBP1). We genetically engineered a mouse model by a single insertion of FLAG tag onto the N terminus of endogenous MLKL (<i>Mlkl<sup>FLAG/FLAG</sup></i>), creating an inactive form of MLKL that permits monitoring of phosphorylated MLKL without activating necroptotic cell death. <i>Casp8<sup>-/-</sup>Mlkl<sup>FLAG/FLAG</sup></i> mice were viable and displayed phosphorylated MLKL in a"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Caspase-8 and FADD prevent spontaneous ZBP1 expression and necroptosis."],"pmcid":["PMC9565532"],"funding_grant_id":["CA2311620","R01 AI135025","P30 CA006927","AI44828","CA0211765","CA006927","AI144400","AI135025","P30 CA021765","R01 AI144400","R01 AI044828","R35 CA231620","R37 AI044828","KA 4830/1-1"],"pubmed_authors":["Kalkavan H","Pelletier S","Quarato G","Liedmann S","Tummers B","Balachandran S","Guy C","Zhang T","Chen MJ","Shaw JJP","Rodriguez DA","Crawford JC","Fitzgerald P","Green DR","Palacios G"],"additional_accession":[]},"is_claimable":false,"name":"Caspase-8 and FADD prevent spontaneous ZBP1 expression and necroptosis.","description":"The absence of Caspase-8 or its adapter, Fas-associated death domain (FADD), results in activation of receptor interacting protein kinase-3 (RIPK3)- and mixed-lineage kinase-like (MLKL)-dependent necroptosis in vivo. Here, we show that spontaneous activation of RIPK3, phosphorylation of MLKL, and necroptosis in Caspase-8- or FADD-deficient cells was dependent on the nucleic acid sensor, Z-DNA binding protein-1 (ZBP1). We genetically engineered a mouse model by a single insertion of FLAG tag onto the N terminus of endogenous MLKL (<i>Mlkl<sup>FLAG/FLAG</sup></i>), creating an inactive form of MLKL that permits monitoring of phosphorylated MLKL without activating necroptotic cell death. <i>Casp8<sup>-/-</sup>Mlkl<sup>FLAG/FLAG</sup></i> mice were viable and displayed phosphorylated MLKL in a","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Oct","modification":"2026-07-14T19:05:47.067Z","creation":"2025-04-07T03:15:37.626Z"},"accession":"S-EPMC9565532","cross_references":{"pubmed":["36191211"],"doi":["10.1073/pnas.2207240119"]}}