School of Medicine, Anhui University of Science and Technology, Huainan, 232001, China.
Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, School of Life Sciences and Technology, Tongji University, 200092, Shanghai, China.
Biochem Biophys Res Commun. 2019 Jun 30;514(3):659-664. doi: 10.1016/j.bbrc.2019.05.022. Epub 2019 May 8.
cGAS-STING (stimulator of interferon genes) signaling is crucial for the recognition of cytoplasmic double-stranded DNA by host cells and consequently activating innate immune response by promoting the production cGAMP and type I interferon. However, it remains elusive how the cGAS enzymatic activity is regulated dynamically. In this study, we identified TRAF6 as a regulator of cGAS mediated anti-viral innate immunity. Our data showed that either ectopic expression or knockdown of TRAF6 modulates the double strand DNA induced expression of interferon-responsive genes. Mechanistically, TRAF6 specifically promotes cGAS activation by targeting cGAS for ubiquitination. Knockdown of TRAF6 results in a decrease in cGAS-induced IFNβ production when cells were infected with herpes simplex virus-1 (HSV-1). Together, our data identified TRAF6 as a positive regulator of cGAS-STING pathway by regulating cGAS activity.
cGAS-STING（干扰素基因刺激物）信号通路对于宿主细胞识别细胞质中的双链 DNA 至关重要，并通过促进 cGAMP 和 I 型干扰素的产生来激活先天免疫反应。然而，cGAS 酶活性如何动态调节仍不清楚。在这项研究中，我们鉴定了 TRAF6 是 cGAS 介导的抗病毒先天免疫的调节剂。我们的数据表明，TRAF6 的异位表达或敲低均可调节双链 DNA 诱导的干扰素反应基因的表达。在机制上，TRAF6 通过靶向 cGAS 进行泛素化来特异性地促进 cGAS 的激活。当细胞感染单纯疱疹病毒-1（HSV-1）时，TRAF6 的敲低会导致 cGAS 诱导的 IFNβ 产生减少。总之，我们的数据表明，TRAF6 通过调节 cGAS 活性，作为 cGAS-STING 通路的正调节剂。
