The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stress.
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.
Pubmed ID: 15073321 RIS Download
Adaptor Proteins, Signal Transducing | Apoptosis | CRADD Signaling Adaptor Protein | Carrier Proteins | Caspase 2 | Caspases | Cell Line | Cell Line, Tumor | Cloning, Molecular | DNA Damage | Death Domain Receptor Signaling Adaptor Proteins | Doxorubicin | Enzyme Activation | Etoposide | Humans | Protein Structure, Tertiary | Proteins | RNA, Small Interfering | Signal Transduction | Transfection | Tumor Suppressor Protein p53