title: TRIM30α Is a Negative-Feedback Regulator of the Intracellular DNA and DNA Virus-Triggered Response by Targeting STING.
abstract: 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.
authors.affiliation: 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.
authors.forename: Yanming
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Qiaoshi
authors.initials: Q
authors.lastname: Lian
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Yan
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Lan
authors.initials: L
authors.lastname: He
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Guomei
authors.initials: G
authors.lastname: Lin
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, China.
authors.forename: Zhexiong
authors.initials: Z
authors.lastname: Lian
authors.affiliation: 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; Peking University-Tsinghua University Joint Center for Life Sciences, Beijing, China.
authors.forename: Zhengfan
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; Key Laboratory of Molecular Virology & Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Sun
mesh_terms: D000818:Animals; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D004267:DNA Viruses / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D007113:Immunity, Innate; D008565:Membrane Proteins / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000276:immunology; D014157:Transcription Factors / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination; D000099197:STING Protein
chemical_list: D004247:DNA; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; C530855:Sting1 protein, mouse; D000099197:STING Protein; C055548:Trim30a protein, mouse