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

Proc Natl Acad Sci U S A. 2005 Oct 4;102(40):14314-20. doi: 10.1073/pnas.0506475102. Epub 2005 Sep 23.

Abstract

The p53 tumor suppressor promotes cell cycle arrest or apoptosis in response to diverse stress stimuli. p53-mediated cell death depends in large part on transcriptional up-regulation of target genes. One of these targets, P53-induced protein with a death domain (PIDD), was shown to function as a mediator of p53-dependent apoptosis. Here we show that PIDD is a cytoplasmic protein, and that PIDD-induced apoptosis and growth suppression in embryonic fibroblasts depend on the adaptor protein receptor-interacting protein (RIP)-associated ICH-1/CED-3 homologous protein with a death domain (RAIDD). We provide evidence that PIDD-induced cell death is associated with the early activation of caspase-2 and later activation of caspase-3 and -7. Our results also show that caspase-2(-/-), in contrast to RAIDD(-/-), mouse embryonic fibroblasts, are only partially resistant to PIDD. Our findings suggest that caspase-2 contributes to PIDD-mediated cell death, but that it is not the sole effector of this pathway.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Apoptosis / physiology*
  • CRADD Signaling Adaptor Protein
  • Carrier Proteins / metabolism*
  • Caspase 2
  • Caspases / metabolism
  • Cells, Cultured
  • Cytoplasm / metabolism
  • Death Domain Receptor Signaling Adaptor Proteins
  • Fibroblasts
  • Fluorescent Antibody Technique
  • Immunoblotting
  • Immunoprecipitation
  • Mice
  • Mice, Knockout

Substances

  • Adaptor Proteins, Signal Transducing
  • CRADD Signaling Adaptor Protein
  • Carrier Proteins
  • Cradd protein, mouse
  • Death Domain Receptor Signaling Adaptor Proteins
  • Pidd1 protein, mouse
  • Caspase 2
  • Caspases