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PIDD mediates NF-κB activation in response to DNA damage

(2005) CELL. 123(6). p.1079-1092
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Abstract
Abstract: Activation of NF-kappa B following genotoxic stress allows time for DNA-damage repair and ensures cell survival accounting for acquired chemoresistance, an impediment to effective cancer therapy. Despite this clinical relevance, little is known about pathways that enable genotoxic-stress-induced NF-kappa B induction. Previously, we reported a role for the p53-inducible death-domain-containing protein, PIDD, in caspase-2 activation and apoptosis in response to DNA damage. We now demonstrate that PIDD plays a critical role in DNA-damage-induced NF-kappa B activation. Upon genotoxic stress, a complex between PIDD, the kinase RIP1, and a component of the NF-kappa B-activating kinase complex, NEMO, is formed. PIDD expression enhances genotoxic-stress-induced NF-kappa B activation through augmented sumoylation and ubiquitination of NEMO. Depletion of PIDD and RIP1, but not caspase-2, abrogates DNA-damage-induced NEMO modification and NF-kappa B activation. We propose that PIDD acts as a molecular switch, controlling the balance between life and death upon DNA damage.
Keywords
DOMAIN-CONTAINING PROTEIN, NECROSIS-FACTOR-ALPHA, TOPOISOMERASE-II, SUMO-1 MODIFICATION, GENOTOXIC STRESS, NEMO/IKK-GAMMA, KINASE RIP, NUCLEAR, COMPLEX, SIGNAL

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Citation

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Chicago
Janssens, Sophie, Antoine Tinel, Saskia Lippens, and Jürg Tschopp. 2005. “PIDD Mediates NF-κB Activation in Response to DNA Damage.” Cell 123 (6): 1079–1092.
APA
Janssens, Sophie, Tinel, A., Lippens, S., & Tschopp, J. (2005). PIDD mediates NF-κB activation in response to DNA damage. CELL, 123(6), 1079–1092.
Vancouver
1.
Janssens S, Tinel A, Lippens S, Tschopp J. PIDD mediates NF-κB activation in response to DNA damage. CELL. 2005;123(6):1079–92.
MLA
Janssens, Sophie, Antoine Tinel, Saskia Lippens, et al. “PIDD Mediates NF-κB Activation in Response to DNA Damage.” CELL 123.6 (2005): 1079–1092. Print.
@article{1202491,
  abstract     = {Abstract: Activation of NF-kappa B following genotoxic stress allows time for DNA-damage repair and ensures cell survival accounting for acquired chemoresistance, an impediment to effective cancer therapy. Despite this clinical relevance, little is known about pathways that enable genotoxic-stress-induced NF-kappa B induction. Previously, we reported a role for the p53-inducible death-domain-containing protein, PIDD, in caspase-2 activation and apoptosis in response to DNA damage. We now demonstrate that PIDD plays a critical role in DNA-damage-induced NF-kappa B activation. Upon genotoxic stress, a complex between PIDD, the kinase RIP1, and a component of the NF-kappa B-activating kinase complex, NEMO, is formed. PIDD expression enhances genotoxic-stress-induced NF-kappa B activation through augmented sumoylation and ubiquitination of NEMO. Depletion of PIDD and RIP1, but not caspase-2, abrogates DNA-damage-induced NEMO modification and NF-kappa B activation. We propose that PIDD acts as a molecular switch, controlling the balance between life and death upon DNA damage.},
  author       = {Janssens, Sophie and Tinel, Antoine and Lippens, Saskia and Tschopp, J{\"u}rg},
  issn         = {0092-8674},
  journal      = {CELL},
  keyword      = {DOMAIN-CONTAINING PROTEIN,NECROSIS-FACTOR-ALPHA,TOPOISOMERASE-II,SUMO-1 MODIFICATION,GENOTOXIC STRESS,NEMO/IKK-GAMMA,KINASE RIP,NUCLEAR,COMPLEX,SIGNAL},
  language     = {eng},
  number       = {6},
  pages        = {1079--1092},
  title        = {PIDD mediates NF-\ensuremath{\kappa}B activation in response to DNA damage},
  url          = {http://dx.doi.org/10.1016/j.cell.2005.09.036},
  volume       = {123},
  year         = {2005},
}

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