Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule.

Article Details

Citation

Holler N, Zaru R, Micheau O, Thome M, Attinger A, Valitutti S, Bodmer JL, Schneider P, Seed B, Tschopp J

Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule.

Nat Immunol. 2000 Dec;1(6):489-95.

PubMed ID
11101870 [ View in PubMed
]
Abstract

Cell death is achieved by two fundamentally different mechanisms: apoptosis and necrosis. Apoptosis is dependent on caspase activation, whereas the caspase-independent necrotic signaling pathway remains largely uncharacterized. We show here that Fas kills activated primary T cells efficiently in the absence of active caspases, which results in necrotic morphological changes and late mitochondrial damage but no cytochrome c release. This Fas ligand-induced caspase-independent death is absent in T cells that are deficient in either Fas-associated death domain (FADD) or receptor-interacting protein (RIP). RIP is also required for necrotic death induced by tumor necrosis factor (TNF) and TNF-related apoptosis-inducing ligand (TRAIL). In contrast to its role in nuclear factor kappa B activation, RIP requires its own kinase activity for death signaling. Thus, Fas, TRAIL and TNF receptors can initiate cell death by two alternative pathways, one relying on caspase-8 and the other dependent on the kinase RIP.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Receptor-interacting serine/threonine-protein kinase 1Q13546Details