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Apoptosis caused by p53-induced protein with death domain (PIDD) depends on the death adapter protein RAIDD

Christina Berube1, Louis-Martin Boucher, Weili Ma

  • 1Ontario Cancer Institute/Princess Margaret Hospital, 610 University Avenue, Toronto, ON, Canada M5G 2M9.

Proceedings of the National Academy of Sciences of the United States of America
|September 27, 2005
PubMed

Insights

The p53 tumor suppressor

Area of Science:

  • Cellular biology
  • Molecular biology
  • Cancer research

Background:

  • The p53 tumor suppressor protein is crucial for cellular responses to stress, inducing cell cycle arrest or apoptosis.
  • p53-mediated apoptosis often involves the transcriptional upregulation of specific target genes, including P53-induced protein with a death domain (PIDD).

Purpose of the Study:

  • To investigate the cellular localization and mechanism of PIDD-induced apoptosis.
  • To determine the role of RAIDD and caspase-2 in PIDD-mediated cell death.

Main Methods:

  • Characterization of PIDD cellular localization.
  • Assessment of PIDD-induced apoptosis and growth suppression in embryonic fibroblasts.
  • Analysis of caspase activation (caspase-2, -3, -7) in response to PIDD.
  • Comparison of PIDD sensitivity in wild-type, RAIDD(-/-), and caspase-2(-/-) mouse embryonic fibroblasts.

Main Results:

  • PIDD functions as a cytoplasmic protein.
  • PIDD-induced apoptosis and growth suppression require the adaptor protein RAIDD.
  • PIDD triggers early caspase-2 activation and subsequent activation of caspase-3 and -7.
  • Caspase-2(-/-) fibroblasts exhibit partial resistance to PIDD, unlike RAIDD(-/-) fibroblasts.

Conclusions:

  • PIDD is a cytoplasmic mediator of p53-dependent apoptosis, requiring RAIDD for its function.
  • Caspase-2 plays a significant, but not exclusive, role in PIDD-mediated cell death.
  • The PIDD pathway involves a complex interplay of caspases, with caspase-2 being a key contributor.

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