The DNA-dependent protein kinase participates in the activation of NF kappa B following DNA damage

Biochem Biophys Res Commun. 1998 Jun 9;247(1):79-83. doi: 10.1006/bbrc.1998.8741.

Abstract

The NFkB transcription factor is activated by diverse stimuli, including Ionizing Radiation (IR) and the cytokine TNF alpha. The role of DNA-PK, a protein kinase involved in the response to DNA damage, in the activation of NF kappa B by IR and TNF alpha was examined. In M059K cells, which express DNA-PK, NF kappa B was activated by both TNF alpha and IR. In M059J cells, which do not express DNA-PK, IR did not activate NF kappa B, whereas TNF alpha induction of NF kappa B was still observed. In HeLa cells, wortmannin, an inhibitor of DNA-PK, blocked the induction of NF kappa B by IR but not by TNF alpha. DNA-PK also phosphorylated the NF kappa B inhibitory proteins IkB-alpha and IkB-beta in vitro, and deletion analysis demonstrated that DNA-PK phosphorylates 2 distinct regions of IkB-beta. These results indicate that DNA-PK participates in the activation of NF kappa B by IR but not by TNF alpha.

Publication types

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

MeSH terms

  • Androstadienes / pharmacology
  • DNA Damage*
  • DNA-Activated Protein Kinase
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Etoposide / pharmacology
  • Gamma Rays
  • Glioma
  • HeLa Cells
  • Humans
  • I-kappa B Proteins*
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • NF-kappa B / radiation effects
  • Nuclear Proteins
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology
  • Wortmannin

Substances

  • Androstadienes
  • DNA-Binding Proteins
  • I kappa B beta protein
  • I-kappa B Proteins
  • NF-kappa B
  • NFKBIA protein, human
  • Nuclear Proteins
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • Etoposide
  • DNA-Activated Protein Kinase
  • PRKDC protein, human
  • Protein-Serine-Threonine Kinases
  • Wortmannin