Abstract
The pivotal discovery that the death proteases caspase 8 (FLICE) and caspase 10 (Mch4/FLICE2) are recruited to the CD-95 and tumor necrosis factor receptor-1 signaling complexes suggested a mechanism used by these cytotoxic receptors to initiate apoptosis. In this report, we describe the cloning and characterization of I-FLICE, a novel inhibitor of tumor necrosis factor receptor-1- and CD-95-induced apoptosis. The overall architecture of I-FLICE is strikingly similar to that of FLICE and Mch4/FLICE2. However, I-FLICE lacks both a catalytic active site and residues that form the substrate binding pocket, in keeping with its dominant negative inhibitory function. I-FLICE is the first example of a catalytically inert caspase that can inhibit apoptosis.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adult
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Amino Acid Sequence
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Antigens, CD / chemistry*
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Apoptosis*
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CASP8 and FADD-Like Apoptosis Regulating Protein
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Carrier Proteins / chemistry
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Caspase 10
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Caspase 8
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Caspase 9
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Caspases*
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Catalysis
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Cell Line
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Cloning, Molecular
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Cysteine Endopeptidases / metabolism
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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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Receptors, Tumor Necrosis Factor / chemistry*
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Receptors, Tumor Necrosis Factor, Type I
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Tissue Distribution
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fas Receptor / metabolism*
Substances
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Antigens, CD
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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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Intracellular Signaling Peptides and Proteins
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Type I
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fas Receptor
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CASP8 protein, human
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CASP9 protein, human
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Caspase 10
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Caspase 8
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Caspase 9
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Caspases
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Cysteine Endopeptidases
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interleukin 1beta-converting enzyme 2
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CASP10 protein, human
Associated data
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GENBANK/AF041458
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GENBANK/AF041459
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GENBANK/AF041460
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GENBANK/AF041461
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GENBANK/AF041462