Immunity：武大舒红兵院士发表抗病毒免疫调控新成果

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在病毒感染过程中，循环GMP-AMP合成酶(cGAS)对胞内DNA的检测，可激活衔接蛋白STING，并触发一种抗病毒反应。然而，目前仍然不确定，是什么机制决定着cGAS-STING通路的激活和失活动力学，从而确保了有效但却可控的先天抗病毒免疫反应。

9月13日，武汉大学生命科学学院舒红兵院士带领的研究小组，在Cell子刊《Immunity》发表题为“Sumoylation Promotes the Stability of the DNA Sensor cGAS and the Adaptor STING to Regulate the Kinetics of Response to DNA Virus”的研究成果。

这项研究发现，在受感染的细胞中和病毒感染早期，泛素连接酶Trim38可靶定cGas用以SUMO化修饰。cGas的SUMO化修饰可阻止其多聚泛素化和降解。在病毒感染早期，Trim38也SUMO化Sting，从而促进Sting激活和蛋白质稳定性。在感染晚期，cGas和Sting被Senp2去SUMO化，随后分别通过白酶体和分子伴侣介导的自噬途径所分解。这些研究结果揭示了Trim38在DNA病毒先天免疫反应中的一个必不可少的作用，并对于确保cGAS-STING通路最佳激活和失活的机制，提供了新的见解。

来源：生物通

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Sumoylation Promotes the Stability of the DNA Sensor cGAS and the Adaptor STING to Regulate the Kinetics of Response to DNA Virus

Ming-Ming Hu1, 2, Qing Yang1, 2, Xue-Qin Xie2, Chen-Yang Liao2, Heng Lin1, Tian-Tian Liu1, 2, Lei Yin1, Hong-Bing Shu

During viral infection, sensing of cytosolic DNA by the cyclic GMP-AMP synthase (cGAS) activates the adaptor protein STING and triggers an antiviral response. Little is known about the mechanisms that determine the kinetics of activation and deactivation of the cGAS-STING pathway, ensuring effective but controlled innate antiviral responses. Here we found that the ubiquitin ligase Trim38 targets cGas for sumoylation in uninfected cells and during the early phase of viral infection. Sumoylation of cGas prevented its polyubiquitination and degradation. Trim38 also sumoylated Sting during the early phase of viral infection, promoting both Sting activation and protein stability. In the late phase of infection, cGas and Sting were desumoylated by Senp2 and subsequently degraded via proteasomal and chaperone-mediated autophagy pathways, respectively. Our findings reveal an essential role for Trim38 in the innate immune response to DNA virus and provide insight into the mechanisms that ensure optimal activation and deactivation of the cGAS-STING pathway.

http://www.sciencedirect.com/sci ... i/S1074761316303387