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. Author manuscript; available in PMC: 2013 Jul 30.
Published in final edited form as: Nat Rev Immunol. 2012 Jan 6;12(2):125–135. doi: 10.1038/nri3133

Figure 3. IL-1R1 signalling regulates type I IFN production.

Figure 3

Interleukin-1 receptor 1 (IL-1R1) signalling positively modulates the production of type I interferons (IFNs) through the differential ubiquitylation of TNF receptor-associated factor 3 (TRAF3). Lysine 48 (K48)-linked polyubiquitylation of TRAF3 leads to its proteosomal degradation and the production of pro-inflammatory cytokines. By contrast, K63-linked polyubiquitylation of TRAF3 triggers the activation of IFN regulatory factor 3 (IRF3) and the subsequent production of type I IFNs. The absence of IL-1 signalling results in increased levels of deubiquitylating enzyme A (DUBA), which cleaves the K63-linked but not the K48-linked ubiquitin chains on TRAF3. LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor-κB; TLR, Toll-like receptor.