State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China; University of Chinese Academy of Sciences, Beijing 100101, China.
State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China; University of Chinese Academy of Sciences, Beijing 100101, China.
J Biol Chem. 2018 Aug 3;293(31):11996-12010. doi: 10.1074/jbc.RA117.001201. Epub 2018 Jun 14.
Chronic neuroinflammation is a characteristic of Parkinson's disease (PD). Previous investigations have shown that Parkin gene mutations are related to the early-onset recessive form of PD and isolated juvenile-onset PD. Further, Parkin plays important roles in mitochondrial quality control and cytokine-induced cell death. However, whether Parkin regulates other cellular events is still largely unknown. In this study, we performed overexpression and knockout experiments and found that Parkin negatively regulates antiviral immune responses against RNA and DNA viruses. Mechanistically, we show that Parkin interacts with tumor necrosis factor receptor-associated factor 3 (TRAF3) to regulate stability of TRAF3 protein by promoting Lys-linked ubiquitination. Our findings suggest that Parkin plays a novel role in innate immune signaling by targeting TRAF3 for degradation and maintaining the balance of innate antiviral immunity.
慢性神经炎症是帕金森病（PD）的特征。先前的研究表明，Parkin 基因突变与早发型隐性 PD 和孤立性少年发病 PD 有关。此外，Parkin 在线粒体质量控制和细胞因子诱导的细胞死亡中发挥重要作用。然而，Parkin 是否调节其他细胞事件在很大程度上仍不清楚。在这项研究中，我们进行了过表达和敲除实验，发现 Parkin 负调控针对 RNA 和 DNA 病毒的抗病毒免疫反应。在机制上，我们表明 Parkin 通过促进 Lys 连接的泛素化与肿瘤坏死因子受体相关因子 3（TRAF3）相互作用，从而调节 TRAF3 蛋白的稳定性。我们的研究结果表明，Parkin 通过靶向 TRAF3 进行降解来在先天免疫信号中发挥新的作用，从而维持先天抗病毒免疫的平衡。
