Research Perspective Volume 3, Issue 10 pp 913—919

Figure 2. A pathway for activation of NF-κB signalling by genotoxic stress (adapted from Hinz et al. [33]). DNA damage recruits and activates PARP-1 and ATM, with PARP-1 producing poly(ADP-ribose) leading to assembly of IKKγ/NEMO and PIASy and ATM. PIASy and ATM SUMOylate and phosphorylate IKKγ/NEMO respectively which is then translocated to the cytoplasm to form the IKK complex. ATM independently translocates to the cytoplasm to induce TRAF6-Ubc13 polyubiquitination, which promotes cIAP dependent IKKγ/NEMO ubiquitination which then promotes TAB2-TAK1 dependent phosphorylation and activation of IKKβ.