title: Ripped to death.
abstract: An old puzzle in the field of cell death was solved recently: the mysterious embryonic lethality of animals deficient in caspase-8 or Fas-associated death domain (FADD), proteins involved in a pathway of apoptosis. This lethality is caused by a failure to develop the yolk sac vasculature rather than a lack of apoptosis. Remarkably, development is rescued by ablation of either of two receptor interacting serine-threonine kinases (RIPKs). Despite being well known cell killers, caspase-8 and FADD act together to block RIPK-mediated necrosis. To manifest this newly elucidated pro-survival function, FADD and caspase-8 depend on FLIP(Long), a catalytically inactive caspase-8 homolog. In this review, the mechanism by which RIPK necrotic death is inhibited by this trio is discussed, as well as how RIPKs might themselves mediate cell death.
authors: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Ricardo
authors: R
authors: Weinlich
authors: Christopher P
authors: CP
authors: Dillon
authors: Douglas R
authors: DR
authors: Green
mesh_terms: D000818:Animals; D017209:Apoptosis; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D006801:Humans; D009336:Necrosis / Q000201:enzymology*; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D053200:Fas-Associated Death Domain Protein; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D053181:Caspase 8