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

AUTOR(ES)

Berube, Christina

FONTE

National Academy of Sciences

RESUMO

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.

Documentos Relacionados

• Lysosomal destabilization in p53-induced apoptosis
• Inhibition of p53-induced apoptosis without affecting expression of p53-regulated genes
• Apoptosis Induced by the Nuclear Death Domain Protein p84N5 Is Inhibited by Association with Rb Protein
• Cell cycle analysis of p53-induced cell death in murine erythroleukemia cells.
• The p53-induced mouse zinc finger protein wig-1 binds double-stranded RNA with high affinity