{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Li X"],"funding":["National Natural Science Foundation of China"],"pagination":["1500-1512"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9345959"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["29(8)"],"pubmed_abstract":["Caspase-8 is an initiator of death receptor-induced apoptosis and an inhibitor of RIPK3-MLKL-dependent necroptosis. In addition, caspase-8 has been implicated in diseases such as lymphoproliferation, immunodeficiency, and autoimmunity in humans. Although auto-cleavage is indispensable for caspase-8 activation, its physiological functions remain poorly understood. Here, we generated a caspase-8 mutant lacking E385 in auto-cleavage site knock-in mouse (Casp8<sup>ΔE385/ΔE385</sup>). Casp8<sup>ΔE385/ΔE385</sup> cells were expectedly resistant to Fas-induced apoptosis, however, Casp8<sup>ΔE385/ΔE385</sup> cells could switch TNF-α-induced apoptosis to necroptosis by attenuating RIPK1 cleavage. More importantly, CASP8(ΔE385) sensitized cells to RIPK3-MLKL-dependent necroptosis through promoting c"],"journal":["Cell death and differentiation"],"pubmed_title":["Caspase-8 auto-cleavage regulates programmed cell death and collaborates with RIPK3/MLKL to prevent lymphopenia."],"pmcid":["PMC9345959"],"funding_grant_id":["31771537","82001684","31970688"],"pubmed_authors":["Liu J","Li J","Li F","Zhang H","Deng J","Li M","Zhao Y","Wang L","Li X","Xing M","Zhao Q","Zhang Y","Zhang X","Ou Y","Luo Y","Wang X","Wu X"],"additional_accession":[]},"is_claimable":false,"name":"Caspase-8 auto-cleavage regulates programmed cell death and collaborates with RIPK3/MLKL to prevent lymphopenia.","description":"Caspase-8 is an initiator of death receptor-induced apoptosis and an inhibitor of RIPK3-MLKL-dependent necroptosis. In addition, caspase-8 has been implicated in diseases such as lymphoproliferation, immunodeficiency, and autoimmunity in humans. Although auto-cleavage is indispensable for caspase-8 activation, its physiological functions remain poorly understood. Here, we generated a caspase-8 mutant lacking E385 in auto-cleavage site knock-in mouse (Casp8<sup>ΔE385/ΔE385</sup>). Casp8<sup>ΔE385/ΔE385</sup> cells were expectedly resistant to Fas-induced apoptosis, however, Casp8<sup>ΔE385/ΔE385</sup> cells could switch TNF-α-induced apoptosis to necroptosis by attenuating RIPK1 cleavage. More importantly, CASP8(ΔE385) sensitized cells to RIPK3-MLKL-dependent necroptosis through promoting c","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Aug","modification":"2025-04-26T11:57:09.635Z","creation":"2025-02-19T05:06:14.828Z"},"accession":"S-EPMC9345959","cross_references":{"pubmed":["35064213"],"doi":["10.1038/s41418-022-00938-9"]}}