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Zebrafish MVP Recruits and Degrades TBK1 To Suppress IFN Production
Li, Shun1,2; Lu, Long-Feng1; Li, Zhuo-Cong1,3; Zhang, Can1,3; Zhou, Xiao-Yu1,3; Zhou, Yu1,3; Zhang, Yong-An1,2,4
Corresponding AuthorZhang, Yong-An(yzhang@ihb.ac.cn)
2019-01-15
Source PublicationJOURNAL OF IMMUNOLOGY
ISSN0022-1767
Volume202Issue:2Pages:559-566
AbstractIFN production is crucial for hosts to defend against viral infection, yet it must be tightly controlled to maintain immune homeostasis. TANK-binding kinase 1 (TBK1) is a pivotal kinase in the IFN induction signaling pathway, but it is negatively regulated by multiple molecules to avoid the excessive expression of IFN in mammals. However, the identified TBK1 suppressors and the mechanisms are rare in fish. In this study, we show that zebrafish major vault protein (MVP) recruits and degrades TBK1 in a lysosome-dependent manner to inhibit IFN production. Through viral infection, polyinosinic: polycytidylic acid and RIG-I-like receptor factor stimulation upregulated IFN expression, but overexpression of MVP significantly subverted these inductions. On the protein level, MVP interacted with TBK1, and interestingly, MVP recruited TBK1 from a uniformly distributed state in the cytoplasm to an aggregated state. Finally, MVP mediated the lysosome-dependent degradation of TBK1 and decreased the IFN response and IFN-stimulated genes expression. Our findings reveal that zebrafish MVP is a negative regulator of IFN production by restricting the activation of TBK1, supplying evidence of the balanced mechanisms of IFN expression in lower vertebrates.
DOI10.4049/jimmunol.1801325
Funding OrganizationNational Natural Science Foundation of China ; Science Fund for Creative Research Groups of the Natural Science Foundation of Hubei Province of China ; National Natural Science Foundation of China ; Science Fund for Creative Research Groups of the Natural Science Foundation of Hubei Province of China
Indexed BySCI ; SCI
Language英语
Funding ProjectNational Natural Science Foundation of China[31502200] ; National Natural Science Foundation of China[31802338] ; National Natural Science Foundation of China[31725026] ; Science Fund for Creative Research Groups of the Natural Science Foundation of Hubei Province of China[2018CFA011]
WOS Research AreaImmunology
WOS SubjectImmunology
WOS IDWOS:000455041800026
WOS KeywordPATTERN-RECOGNITION RECEPTORS ; I INTERFERON ; RIG-I ; PATHOGEN RECOGNITION ; ANTIVIRAL RESPONSE ; ADAPTER PROTEIN ; INDUCTION ; GENE ; ROLES ; BETA
PublisherAMER ASSOC IMMUNOLOGISTS
Funding OrganizationNational Natural Science Foundation of China ; Science Fund for Creative Research Groups of the Natural Science Foundation of Hubei Province of China ; National Natural Science Foundation of China ; Science Fund for Creative Research Groups of the Natural Science Foundation of Hubei Province of China
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Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/28805
Corresponding AuthorZhang, Yong-An
Affiliation1.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Hubei, Peoples R China
2.Qingdao Natl Lab Marine Sci & Technol, Lab Marine Biol & Biotechnol, Qingdao 266071, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Huazhong Agr Univ, Coll Fisheries, State Key Lab Agr Microbiol, Wuhan 43007, Hubei, Peoples R China
Recommended Citation
GB/T 7714
Li, Shun,Lu, Long-Feng,Li, Zhuo-Cong,et al. Zebrafish MVP Recruits and Degrades TBK1 To Suppress IFN Production[J]. JOURNAL OF IMMUNOLOGY,2019,202(2):559-566.
APA Li, Shun.,Lu, Long-Feng.,Li, Zhuo-Cong.,Zhang, Can.,Zhou, Xiao-Yu.,...&Zhang, Yong-An.(2019).Zebrafish MVP Recruits and Degrades TBK1 To Suppress IFN Production.JOURNAL OF IMMUNOLOGY,202(2),559-566.
MLA Li, Shun,et al."Zebrafish MVP Recruits and Degrades TBK1 To Suppress IFN Production".JOURNAL OF IMMUNOLOGY 202.2(2019):559-566.
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