Cited by 176NF-κB Signaling PathwaysDNA Repair MechanismsEffects of Radiation Exposure

The ATM protein is required for sustained activation of NF-κB following DNA damage

Piret, Bernard, Schoonbroodt, Sonia, Piette, Jacques·1999·Oncogene

Abstract

Cells lacking an intact ATM gene are hypersensitive to ionizing radiation and show multiple defects in the cell cycle-coupled checkpoints. DNA damage usually triggers cell cycle arrest through, among other things, the activation of p53. Another DNA-damage responsive factor is NF-kappaB. It is activated by various stress situations, including oxidative stress, and by DNA-damaging compounds such as topoisomerase poisons. We found that cells from Ataxia Telangiectasia patients exhibit a defect in NF-kappaB activation in response to treatment with camptothecin, a topoisomerase I poison. In AT cells, this activation is shortened or suppressed, compared to that observed in normal cells. Ectopic expression of the ATM protein in AT cells increases the activation of NF-kappaB in response to camptothecin. MO59J glioblastoma cells that do not express the DNA-PK catalytic subunit respond normally to camptothecin. These results support the hypothesis that NF-kappaB is a DNA damage-responsive transcription factor and that its activation pathway by DNA damage shares some components with the one leading to p53 activation.

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Crossref · 10.1038/sj.onc.1202541

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  • In AT fibroblasts, NF-kB is activated in an ATM-dependent manner following treatment with a radiomimetic, ionizing radiation, or topoisomerase inhibitor.

    “Previous work with AT fibroblasts had shown that the canonical immune transcription factor NF‐kB is activated in an ATM‐dependent manner following treatment with a radiomimetic, ionizing radiation, or topoisomerase inhibitor (Lee et al, 1998; Piret et al, 1999; Li et al, 2001).”

    From Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease (2022) · cites this paper as Piret et al, 1999

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Authors
Piret, B., Schoonbroodt, S., & Piette, J.
Affiliations
University of Liège (BE)
Venue
Oncogene
Published
1999-04-01
Volume
18
Issue
13
Pages
2261-2271
ISSN
  • 0950-9232 (ISSN-L)
  • 1476-5594
OpenAlex
W2316716290
Cited by
176
References
96
Citations by year
2025: 4 · 2024: 5 · 2023: 2 · 2022: 6 · 2021: 4 · 2020: 5 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 10 · 2015: 11 · 2014: 2 · 2013: 5 · 2012: 9
FWCI
3.21
Type
journal article
Language
en
Open access
closed
Locations
  • Oncogene (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
Keywords
ATM protein, NF-κB activation, DNA damage response, camptothecin, topoisomerase I poisons, ataxia telangiectasia, p53, cell cycle checkpoints, radiosensitivity, DNA-dependent protein kinase, transcription factors
MeSH terms
NF-KappaB Inhibitor alpha, Adolescent, Age Factors, Antineoplastic Agents, Phytogenic, Ataxia Telangiectasia, Brain Neoplasms, Camptothecin, Cells, Cultured, Child, Child, Preschool, DNA Damage, DNA-Binding Proteins, Enzyme Inhibitors, Fibroblasts, Gene Expression Regulation, Glioblastoma, Humans, Leupeptins, Nuclear Proteins, Phosphoric Monoester Hydrolases, Protease Inhibitors, Proteins, Radiation Tolerance, Recombinant Fusion Proteins, Transcription, Genetic, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha, Tumor Suppressor Protein p53, NF-kappa B, Protein Serine-Threonine Kinases, Cell Cycle Proteins, I-kappa B Proteins, Tumor Suppressor Proteins, DNA-Activated Protein Kinase, Topoisomerase I Inhibitors, Ataxia Telangiectasia Mutated Proteins

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