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Dillon, Christopher P.; Weinlich, Ricardo; Rodriguez, Diego A.; Cripps, James G.; Quarato, Giovanni; Gurung, Prajwal; Verbist, Katherine C.; Brewer, Taylor L.; Llambi, Fabien; Gong, Yi-Nan; Janke, Laura J.; Kelliher, Michelle A.; Kanneganti, Thirumala-Devi; Green, Douglas R.
Cell, 05/2014, Letnik: 157, Številka: 5Journal Article
Receptor-interacting protein kinase (RIPK)-1 is involved in RIPK3-dependent and -independent signaling pathways leading to cell death and/or inflammation. Genetic ablation of ripk1 causes postnatal lethality, which was not prevented by deletion of ripk3, caspase-8, or fadd. However, animals that lack RIPK1, RIPK3, and either caspase-8 or FADD survived weaning and matured normally. RIPK1 functions in vitro to limit caspase-8-dependent, TNFR-induced apoptosis, and animals lacking RIPK1, RIPK3, and TNFR1 survive to adulthood. The role of RIPK3 in promoting lethality in ripk1−/− mice suggests that RIPK3 activation is inhibited by RIPK1 postbirth. Whereas TNFR-induced RIPK3-dependent necroptosis requires RIPK1, cells lacking RIPK1 were sensitized to necroptosis triggered by poly I:C or interferons. Disruption of TLR (TRIF) or type I interferon (IFNAR) signaling delayed lethality in ripk1−/−tnfr1−/− mice. These results clarify the complex roles for RIPK1 in postnatal life and provide insights into the regulation of FADD-caspase-8 and RIPK3-MLKL signaling by RIPK1. Display omitted •Lethality in ripk1−/− mice is rescued by ablation of ripk3 with either casp8 or fadd•TNF induces apoptosis, and TRIF or IFN induce necroptosis in ripk1−/− cells•Ripk1−/−ripk3−/−tnfr1−/− mice reach adulthood•Lethality in ripk1−/− mice is delayed by deleting tnfr1 with either trif or ifnar Genetic ablation of RIPK-1 causes postnatal lethality, which is prevented by deletion of RIPK3 together with caspase-8, FADD, or TNFR1. The role of RIPK3 in promoting lethality in ripk1−/− mice suggests that RIPK3 activation is inhibited by RIPK1 postbirth, clarifying the complex roles for RIPK1 in postnatal life.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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