Sumoylation Promotes the Stability of the DNA Sensor cGAS and the Adaptor STING to Regulate the Kinetics of Response to DNA Virus.
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Immunity.       2016 Sep 20;45(3):555-69. doi: 10.1016/j.immuni.2016.08.014. Epub 2016 Sep 13.

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

Hu MM 1, Yang Q 1, Xie XQ 2, Liao CY 2, Lin H 3, Liu TT 1, Yin L 3, Shu HB 4.

Author information

  • 1College of Life Sciences, Wuhan University, Wuhan, China, 430072; Medical Research Institute, Wuhan University, Wuhan, China, 430072.

  • 2Medical Research Institute, Wuhan University, Wuhan, China, 430072.

  • 3College of Life Sciences, Wuhan University, Wuhan, China, 430072.

  • 4College of Life Sciences, Wuhan University, Wuhan, China, 430072; Medical Research Institute, Wuhan University, Wuhan, China, 430072; Collaborative Innovation Center for Viral Immunology, Wuhan University, Wuhan, China, 430072. Electronic address: shuh@whu.edu.cn.

Abstract

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.         

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10.1016

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