The DNA-Dependent Protein Kinase Participates in the Activation of NFκB Following DNA Damage

Abstract

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