title: E3 ubiquitin ligase RNF128 promotes innate antiviral immunity through K63-linked ubiquitination of TBK1.
abstract: TBK1 is essential for interferon-β (IFN-β) production and innate antiviral immunity. Here we identified the T cell anergy-related E3 ubiquitin ligase RNF128 as a positive regulator of TBK1 activation. RNF128 directly interacted with TBK1 through its protease-associated (PA) domain and catalyzed the K63-linked polyubiquitination of TBK1, which led to TBK1 activation, IRF3 activation and IFN-β production. Deficiency of RNF128 expression attenuated IRF3 activation, IFN-β production and innate antiviral immune responses to RNA and DNA viruses, in vitro and in vivo. Our study identified RNF128 as an E3 ligase for K63-linked ubiquitination and activation of TBK1 and delineated a previously unrecognized function for RNF128.
authors: Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University the School of Medicine, Jinan, China.|Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, China.
authors: Guanhua
authors: G
authors: Song
authors: Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University the School of Medicine, Jinan, China.
authors: Bingyu
authors: B
authors: Liu
authors: Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, China.
authors: Zhihui
authors: Z
authors: Li
authors: Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University the School of Medicine, Jinan, China.
authors: Haifeng
authors: H
authors: Wu
authors: Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University the School of Medicine, Jinan, China.
authors: Peng
authors: P
authors: Wang
authors: Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University the School of Medicine, Jinan, China.
authors: Kai
authors: K
authors: Zhao
authors: Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, China.
authors: Guosheng
authors: G
authors: Jiang
authors: Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University the School of Medicine, Jinan, China.
authors: Lei
authors: L
authors: Zhang
authors: Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University the School of Medicine, Jinan, China.
authors: Chengjiang
authors: C
authors: Gao
mesh_terms: D000818:Animals; D005260:Female; D057809:HEK293 Cells; D006561:Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D054243:Vesicular Stomatitis / Q000276:immunology*; D018116:Vesiculovirus / Q000276:immunology*
chemical_list: C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D034741:RNA, Small Interfering; D016899:Interferon-beta; C520250:RNF128 protein, human; C000619695:RNF128 protein, mouse; D044767:Ubiquitin-Protein Ligases; C498588:Tbk1 protein, mouse; D017346:Protein Serine-Threonine Kinases