FIGURE 4 | Ubiquitin conjugation regulates NF-B activation.

Triggering of various cell-surface receptors leads to assembly of a multimolecular complex that includes the RING (really interesting new gene)-type E3 ligase TRAF6 (tumour-necrosis-factor receptor (TNFR)-associated factor 6). TRAF6 recruits the ubiquitin-loaded E2 ubiquitin-conjugating enzyme 13 (UBC13) and promotes K63 (Lys63)-linked polyubiquitylation of IKK- (inhibitor of NF-B (IB) kinase-) and activation of the IKK complex. Phosphorylation of IB by the IKK complex recruits an SCF complex (S-phase kinase-associated protein 1 (SKP1)–cullin-1 (CUL1)–F-box-protein complex), which is an E3 ligase that induces K48-linked polyubiquitylation of IB. This results in the proteasome-dependent degradation of IB and the release of NF-B (nuclear factor-B), which is required for the transactivation of genes by NF-B. BCL-10, B-cell lymphoma 10; CARMA1, caspase-recruitment domain (CARD)–membrane-associated guanylate kinase (MAGUK) protein 1; IL-1R, interleukin-1 receptor; IRAK, IL-1R-associated kinase; MALT1, mucosa-associated-lymphoid-tissue lymphoma-translocation gene 1; MyD88, myeloid differentiation primary-response protein 88; PDK1, 3-phosphoinositide-dependent protein kinase 1; PKC-, protein kinase C-; RIP1, receptor-interacting protein 1; TCR, T-cell receptor; TLR, Toll-like receptor; TRADD, TNFR-associated via death domain; TRIF, Toll/IL-1R (TIR)-domain-containing adaptor protein inducing interferon-.

Download file

If the slide opens in your browser, select "File > Save As" to save it.