苏素化修饰促进DNA传感器cGAS和适配器的稳定性从而调节DNA病毒反应的动力学  

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

作　　者：Ming-Ming Hu Qing Yang Xue-Qin Xie Chen-Yang Liao Heng Lin Tian-Tian Liu Lei Yin 舒红兵[2,3] 

机构地区：[1]不详 [2]中国科学院 [3]武汉大学

出　　处：《科学新闻》2017年第4期52-52,共1页Science News

基　　金：国家重大科学研究计划;国家自然科学基金创新研究群体和重点项目的资助下完成

摘　　要：在病毒感染过程中，宿主可通过环化GMP-AMP合成酶（cGAS）感测细胞溶质中的病毒DNA，激活接头蛋白STING并引发抗病毒反应。然而，我们对于影响cGAS-STING途径的激活和抑制过程的动力学机制知之甚少。该机制对于同时确保先天抗病毒反应的有效性和可控性非常重要。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.

关 键 词：病毒感染 动力学机制 DNA 反应 稳定性 适配器 传感器 修饰 

分 类 号：TP334.7[自动化与计算机技术—计算机系统结构]