Figure 5.

FAT10 stimulates the activity of OTUB1 in deubiquitylating TRAF3. 1. dsRNA is sensed by the cytosolic RNA sensor RIG-I and by the endosomal receptor TLR3, resulting in the activation of TRAF3 by K63-linked autoubiquitylation. 2. FAT10 is expressed upon TNFα/IFN-γ stimulation and interacts with the deubiquitylating enzyme OTUB1. This non-covalent interaction enhances the activity of OTUB1, which becomes more efficient in removing K63-linked ubiquitin from TRAF3. 3. The deubiquitylation of TRAF3 counteracts the optimal continuation of the type-I interferon response, possibly resulting in an attenuated anti-viral response.