RIPK1 blocks early postnatal lethality mediated by caspase-8 and RIPK3.
Cell
; 157(5): 1189-202, 2014 May 22.
Article
en En
| MEDLINE
| ID: mdl-24813850
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 IC 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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Caspasa 8
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Proteína Serina-Treonina Quinasas de Interacción con Receptores
/
Genes Letales
Límite:
Animals
Idioma:
En
Revista:
Cell
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos