DNA damage- and stress-induced apoptosis occurs independently of PIDD.
The p53-induced protein with a death domain, PIDD, was identified as a p53 target gene whose main role is to execute apoptosis in a p53-dependent manner. To investigate the physiological role of PIDD in apoptosis, we generated PIDD-deficient mice. Here, we report that, although PIDD expression is inducible upon DNA damage, PIDD-deficient mice undergo apoptosis normally not only in response to DNA damage, but also in response to various p53-independent stress signals and to death receptor (DR) engagement. This indicates that PIDD is not required for DNA damage-, stress-, and DR-induced apoptosis. Also, in the absence of PIDD, both caspase-2 processing and activation occur in response to DNA damage. Our findings demonstrate that PIDD does not play an essential role for all p53-mediated or p53-independent apoptotic pathways.
Kim
Ira R
IR
Department of Medical Biophysics, University of Toronto, ON, Canada.
Murakami
Kiichi
K
Chen
Nien-Jung
NJ
Saibil
Samuel D
SD
Matysiak-Zablocki
Elzbieta
E
Elford
Alisha R
AR
Bonnard
Madeleine
M
Benchimol
Samuel
S
Jurisicova
Andrea
A
Yeh
Wen-Chen
WC
Ohashi
Pamela S
PS
D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism*; D053143:Caspase 2 / Q000378:metabolism; D004249:DNA Damage; D053418:Death Domain Receptor Signaling Adaptor Proteins; D018390:Gene Targeting; D020287:In Situ Nick-End Labeling; D051379:Mice; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D013312:Stress, Physiological; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014916:Whole-Body Irradiation
D002352:Carrier Proteins; D053418:Death Domain Receptor Signaling Adaptor Proteins; C414729:Pidd1 protein, mouse; D016159:Tumor Suppressor Protein p53; D053143:Caspase 2