Apoptosis caused by p53-induced protein with death domain (PIDD) depends on the death adapter protein RAIDD.
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.
Berube
Christina
C
Ontario Cancer Institute/Princess Margaret Hospital, 610 University Avenue, Toronto, ON, Canada M5G 2M9.
Boucher
Louis-Martin
LM
Ma
Weili
W
Wakeham
Andrew
A
Salmena
Leonardo
L
Hakem
Razqallah
R
Yeh
Wen-Chen
WC
Mak
Tak W
TW
Benchimol
Samuel
S
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053420:CRADD Signaling Adaptor Protein; D002352:Carrier Proteins / Q000378:metabolism*; D053143:Caspase 2; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D053418:Death Domain Receptor Signaling Adaptor Proteins; D005347:Fibroblasts; D005455:Fluorescent Antibody Technique; D015151:Immunoblotting; D047468:Immunoprecipitation; D051379:Mice; D018345:Mice, Knockout
D048868:Adaptor Proteins, Signal Transducing; D053420:CRADD Signaling Adaptor Protein; D002352:Carrier Proteins; C484481:Cradd protein, mouse; D053418:Death Domain Receptor Signaling Adaptor Proteins; C414729:Pidd1 protein, mouse; D053143:Caspase 2; D020169:Caspases