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. 2016 Oct 11;473(20):3401–3419. doi: 10.1042/BCJ20160028

Figure 5. LUBAC and UBE2L3 regulate NF-κB response.

Figure 5.

(A) Cytokine/receptor-mediated activation of LUBAC/UBE2L3 triggers linear (Met1) polyubiquitination of NEMO required for IKK kinase activation. IKK phosphorylates the NF-κB sequestration protein IκBα that is then recognized by SCF/β-TrCP ligase for Lys48 polyubiquitination and subsequent degradation by the proteasome. Released NF-κB translocates to the nucleus to transactivate NF-κB response genes. (B) Model for hyperactivation (indicated by red arrows) of the NF-κB pathway in patients carrying UBE2L3 risk alleles associated with autoimmune diseases. UBE2L3 SNP rs140490 correlates with increased levels of UBE2L3 protein, causing enhanced LUBAC signalling, accelerated IκBα degradation, and hyperactive NF-κB response.