| Literature DB >> 24813850 |
Christopher P Dillon1, Ricardo Weinlich1, Diego A Rodriguez1, James G Cripps1, Giovanni Quarato1, Prajwal Gurung1, Katherine C Verbist1, Taylor L Brewer1, Fabien Llambi1, Yi-Nan Gong1, Laura J Janke2, Michelle A Kelliher3, Thirumala-Devi Kanneganti1, Douglas R Green4.
Abstract
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.Entities:
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Year: 2014 PMID： 24813850 PMCID： PMC4068710 DOI： 10.1016/j.cell.2014.04.018
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582