Figure 3.

SUMOylation in the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. The NF-κB pathway is activated by DNA damage. Unlike the canonical NF-κB pathway, NF-κB signaling activated by genotoxicity requires ataxia-telangiectasia mutated (ATM) kinase, which results in the SUMOylation of NF-κB essential modulator (NEMO). Protein inhibitor of activated STAT 4 promotes the SUMOylation of NEMO and RIPK. After SUMOylation, NEMO and receptor-interacting serine/threonine-protein kinase 1 (RIPK) are subsequently ubiquitylated and can then translocate into the cytoplasm to form a complex to recruit transforming growth factor-beta-activated kinase 1 (TAK1). The TAK1 kinase phosphorylates the inhibitor of nuclear factor-κB (IκB) kinase alpha (IKKα) and IKKβ. Following IκBα phosphorylation, p65 and p50 are released and redistributed to nuclear and transcript target proteins. SUMOylation can decrease the NF-κB-dependent gene expression by stabilizing IκBα through competing with ubiquitylation and promoting the nuclear location of IκBα. SENP2 induced by the activated NF-κB pathway can deSUMOylate NEMO and inhibit the subsequent ubiquitylation.