TRIM30α Is a Negative-Feedback Regulator of the Intracellular DNA and DNA Virus-Triggered Response by Targeting STING

PLoS Pathogens

Zhexiong Lian²  Bo Yang²  Yanming Wang²  Lan He²  Guomei Lin²  Zhengfan Jiang³  Qiaoshi Lian³  Shanshan Yan³  Haiyan Zhou³  Bing Sun⁴ 

[1] Peking University-Tsinghua University Joint Center for Life Sciences, Beijing, China;Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China;School of Life Sciences, University of Science and Technology of China, Hefei, China;State Key Laboratory of Protein and Plant Gene Research, Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking University, Beijing, China

关键词: Immunoblot analysis;    Ubiquitination;    Small interfering RNAs;    Immune response;    DNA viruses;    L929 cells;    Transcription factors;    Interferons;   

DOI  :  10.1371/journal.ppat.1005012

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Uncontrolled immune responses to intracellular DNA have been shown to induce autoimmune diseases. Homeostasis regulation of immune responses to cytosolic DNA is critical for limiting the risk of autoimmunity and survival of the host. Here, we report that the E3 ubiquitin ligase tripartite motif protein 30α (TRIM30α) was induced by herpes simplex virus type 1 (HSV-1) infection in dendritic cells (DCs). Knockdown or genetic ablation of TRIM30α augmented the type I IFNs and interleukin-6 response to intracellular DNA and DNA viruses. Trim30α-deficient mice were more resistant to infection by DNA viruses. Biochemical analyses showed that TRIM30α interacted with the stimulator of interferon genes (STING), which is a critical regulator of the DNA-sensing response. Overexpression of TRIM30α promoted the degradation of STING via K48-linked ubiquitination at Lys275 through a proteasome-dependent pathway. These findings indicate that E3 ligase TRIM30α is an important negative-feedback regulator of innate immune responses to DNA viruses by targeting STING.

【 授权许可】

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