Sumoylation Promotes the Stability of the DNA Sensor cGAS and the Adaptor STING to Regulate the Kinetics of Response to DNA Virus
| Autor: | Heng Lin, Xue-Qin Xie, Hong-Bing Shu, Ming-Ming Hu, Qing Yang, Lei Yin, Tian-Tian Liu, Chen-Yang Liao |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Proteasome Endopeptidase Complex Ubiquitin-Protein Ligases Immunology SUMO protein Biology Tripartite Motif Proteins Mice 03 medical and health sciences 0302 clinical medicine Ubiquitin Animals Immunology and Allergy Innate immune system Autophagy DNA Viruses Ubiquitination Membrane Proteins Sumoylation Signal transducing adaptor protein DNA virus DNA Nucleotidyltransferases Molecular biology Immunity Innate eye diseases Ubiquitin ligase Cell biology Cysteine Endopeptidases Kinetics Sting 030104 developmental biology Infectious Diseases Virus Diseases biology.protein Nucleotides Cyclic Carrier Proteins Signal Transduction 030215 immunology |
| Zdroj: | Immunity. 45:555-569 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2016.08.014 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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