Abstract
The inhibitor-of-apoptosis (IAP) family of genes has an evolutionarily conserved role in regulating programmed cell death in animals ranging from insects to humans. Ectopic expression of human IAP proteins can suppress cell death induced by a variety of stimuli, but the mechanism of this inhibition was previously unknown. Here we show that human X-chromosome-linked IAP directly inhibits at least two members of the caspase family of cell-death proteases, caspase-3 and caspase-7. As the caspases are highly conserved throughout the animal kingdom and are the principal effectors of apoptosis, our findings suggest how IAPs might inhibit cell death, providing evidence for a mechanism of action for these mammalian cell-death suppressors.
MeSH terms
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Amino Acid Sequence
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Apoptosis / physiology*
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Caspase 1
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Caspase 3
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Caspase 7
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Caspases*
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Cell Nucleus / metabolism
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Cell-Free System
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Cysteine Endopeptidases / metabolism*
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Cysteine Proteinase Inhibitors / physiology*
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Cytochrome c Group / metabolism
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Cytosol / metabolism
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Enzyme Activation
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Genetic Linkage
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Humans
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Jurkat Cells
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Molecular Sequence Data
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Protein Processing, Post-Translational
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Proteins / genetics
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Proteins / physiology*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-bcl-2*
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Recombinant Proteins / metabolism
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Transfection
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X Chromosome*
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X-Linked Inhibitor of Apoptosis Protein
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bcl-2-Associated X Protein
Substances
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Cysteine Proteinase Inhibitors
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Cytochrome c Group
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Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Recombinant Proteins
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X-Linked Inhibitor of Apoptosis Protein
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XIAP protein, human
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bcl-2-Associated X Protein
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CASP3 protein, human
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CASP7 protein, human
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Caspase 3
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Caspase 7
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Caspases
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Cysteine Endopeptidases
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Caspase 1