title: The kinase CK1ɛ controls the antiviral immune response by phosphorylating the signaling adaptor TRAF3.
abstract: The signaling adaptor TRAF3 is a highly versatile regulator of both innate immunity and adaptive immunity, but how its phosphorylation is regulated is still unknown. Here we report that deficiency in or inhibition of the conserved serine-threonine kinase CK1ɛ suppressed the production of type I interferon in response to viral infection. CK1ɛ interacted with and phosphorylated TRAF3 at Ser349, which thereby promoted the Lys63 (K63)-linked ubiquitination of TRAF3 and subsequent recruitment of the kinase TBK1 to TRAF3. Consequently, CK1ɛ-deficient mice were more susceptible to viral infection. Our findings establish CK1ɛ as a regulator of antiviral innate immune responses and indicate a novel mechanism of immunoregulation that involves CK1ɛ-mediated phosphorylation of TRAF3.
authors.affiliation: Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Yilong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Chenxi
authors.initials: C
authors.lastname: He
authors.affiliation: Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences &Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Dapeng
authors.initials: D
authors.lastname: Yan
authors.affiliation: Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences &Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Haipeng
authors.initials: H
authors.lastname: Liu
authors.affiliation: Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Jianxia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Cao
authors.affiliation: Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Mianyong
authors.initials: M
authors.lastname: Zuo
authors.affiliation: Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ge
authors.affiliation: Department of Chemistry and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Haojie
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Chemistry and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Qinghe
authors.initials: Q
authors.lastname: Tong
authors.affiliation: Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Chengfeng
authors.initials: C
authors.lastname: Qin
authors.affiliation: Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Baoxue
authors.initials: B
authors.lastname: Ge
mesh_terms: D000818:Animals; D048149:Casein Kinase 1 epsilon / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D057809:HEK293 Cells; D006367:HeLa Cells; D006561:Herpes Simplex / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007370:Interferon Type I / Q000096:biosynthesis / Q000276:immunology; D016899:Interferon-beta / Q000096:biosynthesis / Q000276:immunology*; D013058:Mass Spectrometry; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D060888:Real-Time Polymerase Chain Reaction; D018353:Rhabdoviridae Infections / Q000276:immunology; D048008:TNF Receptor-Associated Factor 3 / Q000235:genetics / Q000276:immunology*; D054875:Ubiquitination; D018116:Vesiculovirus / Q000276:immunology; D014901:West Nile Fever / Q000276:immunology; D014902:West Nile virus / Q000276:immunology
chemical_list: D007370:Interferon Type I; D048008:TNF Receptor-Associated Factor 3; D016899:Interferon-beta; C498588:Tbk1 protein, mouse; D048149:Casein Kinase 1 epsilon; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human