Abstract
Mitochondria-mediated apoptosis plays a central role in animal development and tissue homeostasis, and its alteration results in a range of malignant disorders including cancer. Upon apoptotic stimuli, the mitochondrial proteins cytochrome c and Smac/DIABLO are released into the cytosol, where they synergistically activate caspases by activating Apaf-1 and relieving the apoptotic inhibition by IAPs. Recent biochemical and structural studies reveal a molecular basis for these important events and identify an evolutionarily conserved mechanism of apoptosis from fruit flies to mammals.
MeSH terms
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Amino Acid Sequence
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Animals
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Apoptosis Regulatory Proteins
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Apoptosis*
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Apoptotic Protease-Activating Factor 1
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Carrier Proteins / chemistry
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Carrier Proteins / metabolism
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Caspase Inhibitors
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Caspases / chemistry
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Caspases / metabolism
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Conserved Sequence
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Cytochrome c Group / metabolism
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Humans
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Inhibitor of Apoptosis Proteins
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Intracellular Signaling Peptides and Proteins
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Mitochondria / enzymology
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Mitochondria / metabolism*
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Mitochondrial Proteins*
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Models, Molecular
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Molecular Sequence Data
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Proteins / chemistry
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Proteins / metabolism
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Proto-Oncogene Proteins c-bcl-2 / metabolism
Substances
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APAF1 protein, human
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Apoptosis Regulatory Proteins
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Apoptotic Protease-Activating Factor 1
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Carrier Proteins
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Caspase Inhibitors
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Cytochrome c Group
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DIABLO protein, human
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Inhibitor of Apoptosis Proteins
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Intracellular Signaling Peptides and Proteins
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Mitochondrial Proteins
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Proteins
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Proto-Oncogene Proteins c-bcl-2
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Caspases