I-FLICE, a Novel Inhibitor of Tumor Necrosis Factor Receptor-1- and CD-95-induced Apoptosis

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...

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Bibliographic Details
Published in:The Journal of biological chemistry 1997-07, Vol.272 (28), p.17255-17257
Main Authors: Hu, Shimin, Vincenz, Claudius, Ni, Jian, Gentz, Reiner, Dixit, Vishva M.
Format: Article
Language:English
Subjects:
Adult
Amino Acid Sequence
Antigens, CD - chemistry
Apoptosis
Carrier Proteins - chemistry
Carrier Proteins - genetics
Carrier Proteins - metabolism
CASP8 and FADD-Like Apoptosis Regulating Protein
Caspase 10
Caspase 8
Caspase 9
Caspases
Catalysis
Cell Line
Cloning, Molecular
Cysteine Endopeptidases - metabolism
fas Receptor - metabolism
Humans
Intracellular Signaling Peptides and Proteins
Molecular Sequence Data
Receptors, Tumor Necrosis Factor - chemistry
Receptors, Tumor Necrosis Factor, Type I
Tissue Distribution
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.272.28.17255