TRAF3 is dual regulated by DUBA (OTUD5) and TRIAD3A (RNF216). TRAF3 K63-polyubiquitin is removed by DUBA to disrupt TRAF3-TBK1/IKKi interactions. TRAF3 then undergoes a late phase K48-linked polyubiquitination by TRIAD3A, leading to TRAF3 proteasomal degradation. Thus TRIAD3A acts as a E3- ubiquitin ligase that negatively regulates RLR pathway.
ubiquitin protein ligase activity of RNF216 [cytosol]