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, includi ng 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 a ctivation of NF kappa B by IR and TNF alpha was examined. In M059K cel ls, which express DNA-PK, NF kappa B was activated by both TNF alpha a nd IR. In M059J cells, which do not express DNA-PK, IR did not activat e NF kappa B, whereas TNF alpha induction of NF kappa B was still obse rved. In HeLa cells, wortmannin, an inhibitor of DNA-PK, blocked the i nduction of NF kappa B by IR but not by TNF alpha. DNA-PK also phospho rylated the NF kappa B inhibitory proteins IkB-alpha and IkB-beta in v itro, and deletion analysis demonstrated that DNA-PK phosphorylates 2 distinct regions of IkB-beta, These results indicate that DNA-PK parti cipates in the activation of NF kappa B by IR but not by TNF alpha. (C ) 1998 Academic Press.