title: Proliferative versus apoptotic functions of caspase-8 Hetero or homo: the caspase-8 dimer controls cell fate.
abstract: Caspase-8, the initiator of extrinsically-triggered apoptosis, also has important functions in cellular activation and differentiation downstream of a variety of cell surface receptors. It has become increasingly clear that the heterodimer of caspase-8 with the long isoform of cellular FLIP (FLIP(L)) fulfills these pro-survival functions of caspase-8. FLIP(L), a catalytically defective caspase-8 paralog, can interact with caspase-8 to activate its catalytic function. The caspase-8/FLIP(L) heterodimer has a restricted substrate repertoire and does not induce apoptosis. In essence, caspase-8 heterodimerized with FLIP(L) prevents the receptor interacting kinases RIPK1 and -3 from executing the form of cell death known as necroptosis. This review discusses the latest insights in caspase-8 homo- versus heterodimerization and the implication this has for cellular death or survival. This article is part of a Special Issue entitled: Proteolysis 50 years after the discovery of lysosome.
authors.affiliation: Program of Apoptosis and Cell Death Research, Sanford-Burnham Institute, La Jolla, CA 92037, USA. b.j.vanraam@gmail.com
authors.forename: Bram J
authors.initials: BJ
authors.lastname: van Raam
authors.forename: Guy S
authors.initials: GS
authors.lastname: Salvesen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D053181:Caspase 8 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D002384:Catalysis; D049109:Cell Proliferation; D048788:Growth and Development / Q000235:genetics; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D010802:Phylogeny; D055503:Protein Multimerization / Q000502:physiology*
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D053181:Caspase 8