Parkin negatively regulates the antiviral signaling pathway by targeting TRAF3 for degradation
Parkin negatively regulates the antiviral signaling pathway by targeting TRAF3 for degradation
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DOI：
10.1074/jbc.ra117.001201
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发表时间：
2018-06
期刊：
影响因子：
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通讯作者：
Di Xin;Haiyan Gu;Enping Liu;Qinmiao Sun
中科院分区：
文献类型：
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作者：
Di Xin;Haiyan Gu;Enping Liu;Qinmiao Sun
慢性神经炎症是帕金森病（PD）的特征。既往研究表明Parkin基因突变与早发性隐性PD和孤立性青少年型PD相关。此外，帕金在线粒体质量控制和细胞因子诱导的细胞死亡中发挥着重要作用。然而，帕金是否调节其他细胞事件在很大程度上仍然是未知的。在这项研究中，我们进行了过表达和敲除实验，发现帕金负调节抗RNA和DNA病毒的抗病毒免疫反应。从机制上讲，我们发现帕金与肿瘤坏死因子受体相关因子3（TRAF3）相互作用，通过促进Lys48连接的泛素化来调节TRAF3蛋白的稳定性。我们的研究结果表明，Parkin通过靶向TRAF3降解和维持先天抗病毒免疫的平衡，在先天免疫信号传导中发挥着新的作用。
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 Lys48-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.