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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

Authors

  • Tinel A
  • Tschopp J

Journal

Science (New York, N.Y.)

Publication Data

May 7, 2004

Associated Grants

None

Mesh Terms

  • 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