The Ubiquitin E3 Ligase Parkin Inhibits Innate Antiviral Immunity Through K48-Linked Polyubiquitination of RIG-I and MDA5

作者：Lang Bu, Huan Wang, Panpan Hou, Shuting Guo, Miao He, Jingshu Xiao, Ping Li, Yongheng Zhong, Penghui Jia, Yuanyuan Cao, Guanzhan Liang, Chenwei Yang, Lang Chen, Deyin Guo, Chunmei Li · 发表于：Frontiers in Immunology · 年份：2020 · DOI：10.3389/fimmu.2020.01926 · 被引用次数：28 · 研究领域：interferon and immune responses、Autophagy in Disease and Therapy、Ubiquitin and proteasome pathways

Innate immunity is the first-line defense against antiviral or antimicrobial infection. RIG-I and MDA5, which mediate the recognition of pathogen-derived nucleic acids, are essential for production of type I interferons (IFN). Here, we identified mitochondrion depolarization inducer carbonyl cyanide 3-chlorophenylhydrazone (CCCP) inhibited the response and antiviral activity of type I IFN during viral infection. Furthermore, we found that the PTEN-induced putative kinase 1 (PINK1) and the E3 ubiquitin-protein ligase Parkin mediated mitophagy, thus negatively regulating the activation of RIG-I and MDA5. Parkin directly interacted with and catalyzed the K48-linked polyubiquitination and subsequent degradation of RIG-I and MDA5. Thus, we demonstrate that Parkin limits RLR-triggered innate immunity activation, suggesting Parkin as a potential therapeutic target for the control of viral infection.