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.
Tinel
Antoine
A
Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland.
Tschopp
Jürg
J
D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis; D053420:CRADD Signaling Adaptor Protein; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D053143:Caspase 2; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D004249:DNA Damage; D053418:Death Domain Receptor Signaling Adaptor Proteins; D004317:Doxorubicin / Q000494:pharmacology; D004789:Enzyme Activation; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D034741:RNA, Small Interfering; D015398:Signal Transduction; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D053420:CRADD Signaling Adaptor Protein; C104252:CRADD protein, human; D002352:Carrier Proteins; C484481:Cradd protein, mouse; D053418:Death Domain Receptor Signaling Adaptor Proteins; C485896:PIDD1 protein, human; D011506:Proteins; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D005047:Etoposide; D004317:Doxorubicin; D053143:Caspase 2; D020169:Caspases