title: TRIM35 negatively regulates TLR7- and TLR9-mediated type I interferon production by targeting IRF7.
abstract: Toll-like receptor 7 (TLR7) and TLR9 sense viral nucleic acids and induce type I IFN production, which must be properly controlled to avoid autoimmune diseases. Here, we report the negative regulation of TLR7/9-mediated type I IFN production by TRIM35. TRIM35 expression is induced by TLR7/9 stimulation and then interacts with IRF7, which is the master regulator of type I IFN response. Furthermore, TRIM35 promotes the K48-linked ubiquitination of IRF7 and induces its degradation via a proteasome-dependent pathway. Therefore, TRIM35 is a negative feedback regulator of TLR7/9-mediated type I IFN production due to its ability to suppress the stability of IRF7.
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, China.
authors.forename: Yanming
authors.initials: Y
authors.lastname: Wang
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: School of Life Sciences, University of Science and Technology of China, Hefei, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Key Laboratory of Molecular Virology & Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yan
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: 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: Qiaoshi
authors.initials: Q
authors.lastname: Lian
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. Electronic address: bsun@sibs.ac.cn.
authors.forename: Bing
authors.initials: B
authors.lastname: Sun
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D050839:Interferon Regulatory Factor-7 / Q000378:metabolism*; D007370:Interferon Type I / Q000096:biosynthesis*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D046988:Proteasome Endopeptidase Complex; D055550:Protein Stability; D034622:RNA Interference; D034741:RNA, Small Interfering; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D051199:Toll-Like Receptor 7 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D051017:Apoptosis Regulatory Proteins; D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I; C494235:Irf7 protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C000599700:TRIM35 protein, mouse; C477038:Tlr7 protein, mouse; C495370:Tlr9 protein, mouse; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D046988:Proteasome Endopeptidase Complex
keywords: Feedback regulation; IRF7; K48-linked ubiquitination; Proteasome-dependent degradation; TLR7/9; TRIM35