The DNA-dependent protein kinase participates in the activation of NF kappa B following DNA damage.
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.
Basu
S
S
Joint Center for Radiation Therapy, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Rosenzweig
K R
KR
Youmell
M
M
Price
B D
BD
D000730:Androstadienes / Q000494:pharmacology; D004249:DNA Damage; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005047:Etoposide / Q000494:pharmacology; D005720:Gamma Rays; D005910:Glioma; D006367:HeLa Cells; D006801:Humans; D020672:I-kappa B Proteins; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000528:radiation effects; D009687:Nuclear Proteins; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000077191:Wortmannin
D000730:Androstadienes; D004268:DNA-Binding Proteins; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D009687:Nuclear Proteins; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D005047:Etoposide; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases; D000077191:Wortmannin