{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Garnish SE"],"funding":["Department of Health | National Health and Medical Research Council"],"pagination":["6046"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10539340"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(1)"],"pubmed_abstract":["Across the globe, 2-3% of humans carry the p.Ser132Pro single nucleotide polymorphism in MLKL, the terminal effector protein of the inflammatory form of programmed cell death, necroptosis. Here we show that this substitution confers a gain in necroptotic function in human cells, with more rapid accumulation of activated MLKL<sup>S132P</sup> in biological membranes and MLKL<sup>S132P</sup> overriding pharmacological and endogenous inhibition of MLKL. In mouse cells, the equivalent Mlkl S131P mutation confers a gene dosage dependent reduction in sensitivity to TNF-induced necroptosis in both hematopoietic and non-hematopoietic cells, but enhanced sensitivity to IFN-β induced death in non-hematopoietic cells. In vivo, Mlkl<sup>S131P</sup> homozygosity reduces the capacity to clear Salmonella "],"journal":["Nature communications"],"pubmed_title":["A common human MLKL polymorphism confers resistance to negative regulation by phosphorylation."],"pmcid":["PMC10539340"],"funding_grant_id":["1105023","1107149","2002965","1092602","1142669","2011584"],"pubmed_authors":["Horne CR","Young SN","Lawlor KE","Pearson JS","Silke J","Kauppi M","Meng Y","Slade CA","Tovey Crutchfield EC","Frank D","Jacobsen AV","Patel KM","Martin KR","Eng VV","Vinuesa CG","Doerflinger M","Hall C","Garnish SE","Chiou S","Ambrose R","Atkin-Smith GK","Ng AP","Samson AL","Cook M","Wicks IP","Athanasopoulos V","Hildebrand JM","Murphy JM","Di Rago L","Ebert G","Jackson VE"],"additional_accession":[]},"is_claimable":false,"name":"A common human MLKL polymorphism confers resistance to negative regulation by phosphorylation.","description":"Across the globe, 2-3% of humans carry the p.Ser132Pro single nucleotide polymorphism in MLKL, the terminal effector protein of the inflammatory form of programmed cell death, necroptosis. Here we show that this substitution confers a gain in necroptotic function in human cells, with more rapid accumulation of activated MLKL<sup>S132P</sup> in biological membranes and MLKL<sup>S132P</sup> overriding pharmacological and endogenous inhibition of MLKL. In mouse cells, the equivalent Mlkl S131P mutation confers a gene dosage dependent reduction in sensitivity to TNF-induced necroptosis in both hematopoietic and non-hematopoietic cells, but enhanced sensitivity to IFN-β induced death in non-hematopoietic cells. In vivo, Mlkl<sup>S131P</sup> homozygosity reduces the capacity to clear Salmonella ","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Sep","modification":"2026-05-29T01:58:13.345Z","creation":"2024-12-03T23:39:04.303Z"},"accession":"S-EPMC10539340","cross_references":{"pubmed":["37770424"],"doi":["10.1038/s41467-023-41724-6"]}}