Regulation of NFKB by Ubiquitination

Stimulation of cells with IL-1β leads to the activation of the ubiquitin E3 ligase TRAF6, which catalyzes the synthesis of unanchored K63 polyubiquitin chains that bind to the TAB2 subunit of the TAK1 kinase complex, resulting in TAK1 activation. TAK1 then phosphorylates IKKβ, leading to NF-κB activation. In the TNFα pathway, stimulation of the cells leads to the recruitment of several ubiquitin E3 ligases to the receptor, including TRAF2, TRAF5, cIAP1, cIAP2 and LUBAC (consisting of HOIP, HOIL-1, and Sharpin). These E3s and Ubch5 synthesize ubiquitin chains of different linkages, including K63, K11 and linear (M1). The physiological targets of these ubiquitin chains are still not clear, but it is clear that the ubiquitination events lead to TAK1 and IKK activation. Two bacterial proteins, OspI and NleE, are able to inhibit NF-κB activation by targeting Ubc13 and TAB2/3, respectively.

Publication

Regulation of NF-κB by Ubiquitination. () Jueqi Chen, et al. Curr Opin Immunol. ;25(1):4-12. Figure: F1. All organisms Homo sapiens Rattus norvegicus Mus musculus Danio rerio

Disease mentions