Science · 2004 · 659 citations · 19 references
Apoptosis is initiated by clustering of inactive caspases into complexes, and caspase‑2 is recruited into a yet‑unidentified large protein complex that mediates stress‑induced cell death. We demonstrate that caspase‑2 is activated within a PIDD–RAIDD complex, and that elevated PIDD expression drives spontaneous caspase‑2 activation and enhances sensitivity to genotoxic apoptosis, suggesting this complex regulates p53‑dependent cell death.
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.
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Fabio Martinon, Kimberly Burns, Jürg Tschopp · Molecular Cell · 2002 · 5.9K citations · Full text
A Unified Model for Apical Caspase Activation
Kelly M. Boatright, Martin Renatus, Fiona L. Scott et al. · Molecular Cell · 2003 · 941 citations · Full text
Signal Transduction, Molecular Physiology, Signaling Pathway +10