A novel ionizing radiation-induced signaling pathway that activates the transcription factor NF-kappaB

Oncogene. 1998 Oct 8;17(14):1821-6. doi: 10.1038/sj.onc.1202088.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcysteine / metabolism
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins
  • Cell Line
  • DNA-Binding Proteins
  • Enzyme Inhibitors / pharmacology
  • Genistein / pharmacology
  • Humans
  • I-kappa B Kinase
  • NF-kappa B / metabolism*
  • NF-kappa B / radiation effects
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Proteins / metabolism
  • Signal Transduction / radiation effects*
  • Staurosporine / pharmacology
  • Transcriptional Activation
  • Tumor Necrosis Factor-alpha / pharmacology
  • Tumor Suppressor Proteins

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • NF-kappa B
  • Proteins
  • Tumor Necrosis Factor-alpha
  • Tumor Suppressor Proteins
  • Genistein
  • Protein-Tyrosine Kinases
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein-Serine-Threonine Kinases
  • CHUK protein, human
  • I-kappa B Kinase
  • IKBKB protein, human
  • IKBKE protein, human
  • Staurosporine
  • Acetylcysteine