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Science 304 (5672): 843-846

Copyright © 2004 by the American Association for the Advancement of Science

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

Antoine Tinel, and Jürg Tschopp*

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.

Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland.

* To whom correspondence should be addressed. E-mail: jurg.tschopp{at}ib.unil.ch


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