The DOI matches its Crossref record.
A novel ionizing radiation-induced signaling pathway that activates the transcription factor NF-κB
Abstract
The signaling pathway through which ionizing radiation induces NF-kappaB activation is not fully understood. IkappaB-alpha, an inhibitory protein of NF-kappaB mediates the activation of NF-kappaB in response to various stimuli, including cytokines, mitogens, oxidants and other stresses. We have now identified an ionizing radiation-induced signaling pathway that is independent of TNF-alpha. IkappaB-alpha degradation is rapid in response to TNF-alpha induction, but it is absent in response to ionizing radiation exposure in cells from individuals with ataxia-telangiectasia (AT). Overexpression of wild-type ATM, the product of the gene defective in AT patients, restores radiation-induced degradation of IkappaB-alpha. Furthermore, phosphorylation of IkappaB-alpha by immunoprecipitated ATM kinase is increased in control fibroblasts and transfected AT cells following ionizing radiation exposure. These data provide support for a novel ionizing radiation-induced signaling pathway for activation of NF-kappaB and a molecular basis for the sensitivity of AT patients to oxidative stresses.
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“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 Lee et al, 1998
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Phosphorylation meets ubiquitination: the control of NF-κB activity
Karin, M., & Ben-Neriah, Y. (2000) · Annual Review of Immunology · doi:10.1146/annurev.immunol.18.1.621 · Cited by 4,766
Regulation and Function of IKK and IKK-Related Kinases
Häcker, H., & Karin, M. (2006) · Science s STKE · doi:10.1126/stke.3572006re13 · Cited by 1,298
“Genetic evidence shows that the kinase ATM (ataxia telangiectasia mutated) is required for this response, although the mechanism by which it activates NF-κB has been enigmatic (156, 157).”
BackgroundThe many substrates and functions of ATM.
Kastan, M. B., & Lim, D.-S. (2000) · Nature Reviews Molecular Cell Biology · doi:10.1038/35043058 · Cited by 779
Cell Type-Specific Roles of NF-κB Linking Inflammation and Thrombosis
Mussbacher, M., Salzmann, M., Brostjan, C., Hoesel, B., Schoergenhofer, C., Datler, H., Hohensinner, P., Basílio, J., Petzelbauer, P., Assinger, A., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00085 · Cited by 596
“Physical stress Ionizing radiation (67, 68), UV-light (69, 70), cold (71)”
BackgroundThe NF-κB Activation Pathway: A Paradigm in Information Transfer from Membrane to Nucleus
Rothwarf, D., & Karin, M. (1999) · Science's STKE · doi:10.1126/stke.1999.5.re1 · Cited by 553
Metadata
- Authors
- Lee, S.-J., Dimtchev, A., Lavin, M. F., Dritschilo, A., & Jung, M.
- Affiliations
- Georgetown University Medical Center (US)
- QIMR Berghofer Medical Research Institute (AU)
- Venue
- Oncogene
- Published
- 1998-10-08
- Volume
- 17
- Issue
- 14
- Pages
- 1821-1826
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2323797330
- Cited by
- 136
- References
- 0
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 6 · 2016: 4 · 2015: 2 · 2014: 2 · 2013: 5 · 2012: 4
- FWCI
- 3.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1r29ca063023-01, 5r01ca045408-13)
- National Cancer Institute (CA74175, CA63023, CA-45408, P01CA074175)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- ionizing radiation, NF-κB activation, IκBα degradation, ATM kinase, ataxia telangiectasia, IκBα phosphorylation, oxidative stress sensitivity
- MeSH terms
- Acetylcysteine, Cell Line, DNA-Binding Proteins, Enzyme Inhibitors, Humans, Phosphorylation, Protein-Tyrosine Kinases, Proteins, Tumor Necrosis Factor-alpha, Signal Transduction, Transcriptional Activation, NF-kappa B, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Staurosporine, Genistein, Tumor Suppressor Proteins, I-kappa B Kinase, Ataxia Telangiectasia Mutated Proteins
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