The PIDDosome, a Protein Complex Implicated in Activation of Caspase-2 in Response to Genotoxic Stress

作者：Antoine Tinel, Jürg Tschopp · 发表于：Science · 年份：2004 · DOI：10.1126/science.1095432 · 被引用次数：669 · 研究领域：Cell death mechanisms and regulation、Inflammasome and immune disorders、PARP inhibition in cancer therapy

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.