title: Casper is a FADD- and caspase-related inducer of apoptosis.
abstract: Caspases are cysteine proteases that play a central role in apoptosis. Caspase-8 may be the first enzyme of the proteolytic cascade activated by the Fas ligand and tumor necrosis factor (TNF). Caspase-8 is recruited to Fas and TNF receptor-1 (TNF-R1) through interaction of its prodomain with the death effector domain (DED) of the receptor-associating FADD. Here we describe a novel 55 kDa protein, Casper, that has sequence similarity to caspase-8 throughout its length. However, Casper is not a caspase since it lacks several conserved amino acids found in all caspases. Casper interacts with FADD, caspase-8, caspase-3, TRAF1, and TRAF2 through distinct domains. When overexpressed in mammalian cells, Casper potently induces apoptosis. A C-terminal deletion mutant of Casper inhibits TNF- and Fas-induced cell death, suggesting that Casper is involved in these apoptotic pathways.
authors.affiliation: Tularik, Incorporated, South San Francisco, California 94080, USA.
authors.forename: H B
authors.initials: HB
authors.lastname: Shu
authors.forename: D R
authors.initials: DR
authors.lastname: Halpin
authors.forename: D V
authors.initials: DV
authors.lastname: Goeddel
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D017209:Apoptosis; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000378:metabolism* / Q000502:physiology*; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D003001:Cloning, Molecular; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D004790:Enzyme Induction; D053200:Fas-Associated Death Domain Protein; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000378:metabolism; D011994:Recombinant Proteins; D016415:Sequence Alignment; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D015843:Serpins / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014764:Viral Proteins; D019014:fas Receptor / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D011994:Recombinant Proteins; D015843:Serpins; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; D019014:fas Receptor; C074641:interleukin-1beta-converting enzyme inhibitor; D010450:Endopeptidases; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D003546:Cysteine Endopeptidases