title: The FLIP Side of Life.
abstract: The anti-apoptotic protein c-FLIP, a catalytically inactive homolog of caspase-8, is an important regulator of death receptor signaling. Death receptors constitute a subgroup of the tumor necrosis factor receptor (TNFR) superfamily, which includes TNFR1, Fas, DR4, and DR5. When activated by their respective ligands, TNF, Fas ligand (FasL), and TNF-related apoptosis-inducing ligand (TRAIL), these receptors cause caspase-8-mediated apoptosis. If caspase-8 activity is blocked, however, then these receptors promote death by necroptosis (programmed necrosis), which requires the kinases receptor-interacting kinase 1 (RIPK1) and RIPK3, as well as mixed-lineage kinase-like protein. Necroptosis has become the subject of intense research because it promotes inflammation, and inhibiting this pathway can limit extensive tissue damage and even lethality in inflammatory syndromes. A study now reports on the role of c-FLIP in vivo from experiments with a range of conditional knockout mice and demonstrates that c-FLIP plays a critical role in inhibiting both apoptotic and necroptotic cell death within the whole mouse.
authors: Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia. silke@wehi.edu.au
authors: John
authors: J
authors: Silke
authors: Andreas
authors: A
authors: Strasser
mesh_terms: D000818:Animals; D017209:Apoptosis; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000235:genetics / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism; D006801:Humans; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009154:Mutation; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D015398:Signal Transduction; D019014:fas Receptor / Q000378:metabolism
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; C506387:Cflar protein, mouse; D008024:Ligands; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D019014:fas Receptor; D053181:Caspase 8