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p53-induced protein with a death domain (PIDD) isoforms differentially activate nuclear factor-kappaB and caspase-2 in response to genotoxic stress

(2008) ONCOGENE. 27(3). p.387-396
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Abstract
Cellsres pond to DNA damage in a complex way and the fate of damaged cells depends on the balance between pro-and antiapoptotic signals. This is of crucial importance in cancer as genotoxic stress is implied both in oncogenesis and in classical tumor therapies. p53-induced protein with a death domain (PIDD), initially described as a p53-inducible gene, is one of the molecular switches able to activate a survival or apoptotic program. Two isoforms of PIDD, PIDD ( isoform 1) and LRDD ( isoform 2), have already been reported and we describe here a third isoform. These three isoforms are differentially expressed in tissues and cell lines. Genotoxic stress only affects PIDD isoform 3 mRNA levels, whereas isoforms 1 and 2 mRNA levels remain unchanged. All isoforms are capable of activating nuclear factor-kappaB in response to genotoxic stress, but only isoform 1 interacts with RIP-associated ICH-1/CED-3 homologous protein with a death domain and activates caspase-2. Isoform 2 counteracts the pro-apoptotic function of isoform 1, whereas isoform 3 enhances it. Thus, the differential splicing of PIDD mRNA leads to the formation of at least three proteins with antagonizing/agonizing functions, thereby regulating cell fate in response to DNA damage.
Keywords
PIDD, ATM, NEMO, MITOCHONDRIA, INDUCED APOPTOSIS, B ACTIVATION, DNA-DAMAGE, DNA repair, NF-kappa B, caspase-2

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Chicago
Cuenin, S, A Tinel, Sophie Janssens, and J Tschopp. 2008. “P53-induced Protein with a Death Domain (PIDD) Isoforms Differentially Activate Nuclear factor-kappaB and Caspase-2 in Response to Genotoxic Stress.” Oncogene 27 (3): 387–396.
APA
Cuenin, S., Tinel, A., Janssens, S., & Tschopp, J. (2008). p53-induced protein with a death domain (PIDD) isoforms differentially activate nuclear factor-kappaB and caspase-2 in response to genotoxic stress. ONCOGENE, 27(3), 387–396.
Vancouver
1.
Cuenin S, Tinel A, Janssens S, Tschopp J. p53-induced protein with a death domain (PIDD) isoforms differentially activate nuclear factor-kappaB and caspase-2 in response to genotoxic stress. ONCOGENE. 2008;27(3):387–96.
MLA
Cuenin, S, A Tinel, Sophie Janssens, et al. “P53-induced Protein with a Death Domain (PIDD) Isoforms Differentially Activate Nuclear factor-kappaB and Caspase-2 in Response to Genotoxic Stress.” ONCOGENE 27.3 (2008): 387–396. Print.
@article{1202563,
  abstract     = {Cellsres pond to DNA damage in a complex way and the fate of damaged cells depends on the balance between pro-and antiapoptotic signals. This is of crucial importance in cancer as genotoxic stress is implied both in oncogenesis and in classical tumor therapies. p53-induced protein with a death domain (PIDD), initially described as a p53-inducible gene, is one of the molecular switches able to activate a survival or apoptotic program. Two isoforms of PIDD, PIDD ( isoform 1) and LRDD ( isoform 2), have already been reported and we describe here a third isoform. These three isoforms are differentially expressed in tissues and cell lines. Genotoxic stress only affects PIDD isoform 3 mRNA levels, whereas isoforms 1 and 2 mRNA levels remain unchanged. All isoforms are capable of activating nuclear factor-kappaB in response to genotoxic stress, but only isoform 1 interacts with RIP-associated ICH-1/CED-3 homologous protein with a death domain and activates caspase-2. Isoform 2 counteracts the pro-apoptotic function of isoform 1, whereas isoform 3 enhances it. Thus, the differential splicing of PIDD mRNA leads to the formation of at least three proteins with antagonizing/agonizing functions, thereby regulating cell fate in response to DNA damage.},
  author       = {Cuenin, S and Tinel, A and Janssens, Sophie and Tschopp, J},
  issn         = {0950-9232},
  journal      = {ONCOGENE},
  keywords     = {PIDD,ATM,NEMO,MITOCHONDRIA,INDUCED APOPTOSIS,B ACTIVATION,DNA-DAMAGE,DNA repair,NF-kappa B,caspase-2},
  language     = {eng},
  number       = {3},
  pages        = {387--396},
  title        = {p53-induced protein with a death domain (PIDD) isoforms differentially activate nuclear factor-kappaB and caspase-2 in response to genotoxic stress},
  url          = {http://dx.doi.org/10.1038/sj.onc.1210635},
  volume       = {27},
  year         = {2008},
}

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