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.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Apoptosis*
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CASP8 and FADD-Like Apoptosis Regulating Protein
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Carrier Proteins / metabolism*
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Carrier Proteins / physiology*
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Caspase 3
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Caspase 8
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Caspase 9
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Caspases*
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Cloning, Molecular
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Cysteine Endopeptidases / chemistry*
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Cysteine Endopeptidases / metabolism
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Endopeptidases / metabolism
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Enzyme Induction
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Fas-Associated Death Domain Protein
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HeLa Cells
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Humans
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Intracellular Signaling Peptides and Proteins*
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Molecular Sequence Data
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Protein Binding
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Protein Processing, Post-Translational
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Proteins / metabolism
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Recombinant Proteins
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Sequence Alignment
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Sequence Deletion
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Sequence Homology, Amino Acid
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Serpins / metabolism
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Signal Transduction
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Structure-Activity Relationship
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TNF Receptor-Associated Factor 1
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TNF Receptor-Associated Factor 2
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Tumor Necrosis Factor-alpha / physiology*
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Viral Proteins*
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fas Receptor / physiology*
Substances
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Adaptor Proteins, Signal Transducing
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CASP8 and FADD-Like Apoptosis Regulating Protein
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CFLAR protein, human
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Carrier Proteins
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FADD protein, human
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Fas-Associated Death Domain Protein
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Intracellular Signaling Peptides and Proteins
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Proteins
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Recombinant Proteins
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Serpins
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TNF Receptor-Associated Factor 1
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TNF Receptor-Associated Factor 2
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Tumor Necrosis Factor-alpha
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Viral Proteins
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fas Receptor
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interleukin-1beta-converting enzyme inhibitor
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Endopeptidases
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CASP3 protein, human
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CASP8 protein, human
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CASP9 protein, human
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Caspase 3
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Caspase 8
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Caspase 9
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Caspases
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Cysteine Endopeptidases