Fig. 5.

DNA-PK/IKKγ interaction modulates NEMO nuclear translocation. a HEK293 cells were cotransfected with a SUMO-1 plasmid and either wild-type NEMO or mutant NEMO. After exposure to irradiation (IR, 10 Gy), the cells were additionally incubated for 30 min. The lysates were immunoprecipitated (IP) with anti-GFP, followed by immunoblotting (IB) with the indicated antibodies. b Proposed model of DNA-PK function in NF-κB activation by genotoxic stress: Under genotoxic stress, DNA-PK phosphorylates NEMO at Ser43, which allows entry of the protein into the nucleus; then, the SUMO ligase PIASy and the kinase ataxia telangiectasia mutated (ATM) SUMOylate and phosphorylate nuclear IKKγ (NEMO), which results in ubiquitination of NEMO, expulsion from the nucleus and activation of the cytoplasmatic IKK complex [41, 42]