Negative regulation of DDX58/IFIH1 signaling by RNF216

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.

TRAF3 蛋白受到 DUBA（OTUD5）和 TRIAD3A（RNF216）的双重调控。DUBA 通过去除 TRAF3 K63 多聚泛素化修饰，中断 TRAF3 与 TBK1/IKKi 的相互作用。随后，TRAF3 在 TRIAD3A 的作用下，经历晚期 K48 链接的多聚泛素化过程，导致其被蛋白酶体降解。因此，TRIAD3A 作为一种 E3 泛素连接酶，对 RLR 通路发挥负向调控作用。