Abstract
Apoptosis is triggered by activation of initiator caspases upon complex-mediated clustering of the inactive zymogen, as occurs in the caspase-9-activating apoptosome complex. Likewise, caspase-2, which is involved in stress-induced apoptosis, is recruited into a large protein complex, the molecular composition of which remains elusive. We show that activation of caspase-2 occurs in a complex that contains the death domain-containing protein PIDD, whose expression is induced by p53, and the adaptor protein RAIDD. Increased PIDD expression resulted in spontaneous activation of caspase-2 and sensitization to apoptosis by genotoxic stimuli. Because PIDD functions in p53-mediated apoptosis, the complex assembled by PIDD and caspase-2 is likely to regulate apoptosis induced by genotoxins.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Apoptosis*
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CRADD Signaling Adaptor Protein
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Carrier Proteins / chemistry
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Carrier Proteins / metabolism*
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Caspase 2
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Caspases / metabolism*
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Cell Line
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Cell Line, Tumor
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Cloning, Molecular
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DNA Damage*
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Death Domain Receptor Signaling Adaptor Proteins
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Doxorubicin / pharmacology
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Enzyme Activation
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Etoposide / pharmacology
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Humans
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Protein Structure, Tertiary
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Proteins / chemistry
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Proteins / metabolism
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RNA, Small Interfering
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Signal Transduction
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Transfection
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Tumor Suppressor Protein p53 / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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CRADD Signaling Adaptor Protein
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CRADD protein, human
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Carrier Proteins
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Cradd protein, mouse
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Death Domain Receptor Signaling Adaptor Proteins
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PIDD1 protein, human
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Proteins
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RNA, Small Interfering
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Tumor Suppressor Protein p53
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Etoposide
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Doxorubicin
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Caspase 2
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Caspases