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http://purl.uniprot.org/citations/27538435http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/27538435http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/27538435http://www.w3.org/2000/01/rdf-schema#comment"

Background

After viral infection and the stimulation of some pattern-recognition receptors, TANK-binding kinase I (TBK1) is activated by K63-linked polyubiquitination followed by trans-autophosphorylation. While the activated TBK1 induces type I interferon production by phosphorylating the transcription factor IRF3, the precise molecular mechanisms underlying TBK1 activation remain unclear.

Results

We report here the localization of the ubiquitinated and phosphorylated active form of TBK1 to the Golgi apparatus after the stimulation of RIG-I-like receptors (RLRs) or Toll-like receptor-3 (TLR3), due to TBK1 K63-linked ubiquitination on lysine residues 30 and 401. The ubiquitin-binding protein optineurin (OPTN) recruits ubiquitinated TBK1 to the Golgi apparatus, leading to the formation of complexes in which TBK1 is activated by trans-autophosphorylation. Indeed, OPTN deficiency in various cell lines and primary cells impairs TBK1 targeting to the Golgi apparatus and its activation following RLR or TLR3 stimulation. Interestingly, the Bluetongue virus NS3 protein binds OPTN at the Golgi apparatus, neutralizing its activity and thereby decreasing TBK1 activation and downstream signaling.

Conclusions

Our results highlight an unexpected role of the Golgi apparatus in innate immunity as a key subcellular gateway for TBK1 activation after RNA virus infection."xsd:string
http://purl.uniprot.org/citations/27538435http://purl.org/dc/terms/identifier"doi:10.1186/s12915-016-0292-z"xsd:string
http://purl.uniprot.org/citations/27538435http://purl.org/dc/terms/identifier"doi:10.1186/s12915-016-0292-z"xsd:string
http://purl.uniprot.org/citations/27538435http://purl.uniprot.org/core/author"Arnoult D."xsd:string
http://purl.uniprot.org/citations/27538435http://purl.uniprot.org/core/author"Arnoult D."xsd:string
http://purl.uniprot.org/citations/27538435http://purl.uniprot.org/core/author"Garcin D."xsd:string
http://purl.uniprot.org/citations/27538435http://purl.uniprot.org/core/author"Garcin D."xsd:string
http://purl.uniprot.org/citations/27538435http://purl.uniprot.org/core/author"Vitour D."xsd:string
http://purl.uniprot.org/citations/27538435http://purl.uniprot.org/core/author"Vitour D."xsd:string
http://purl.uniprot.org/citations/27538435http://purl.uniprot.org/core/author"Vazquez A."xsd:string
http://purl.uniprot.org/citations/27538435http://purl.uniprot.org/core/author"Vazquez A."xsd:string
http://purl.uniprot.org/citations/27538435http://purl.uniprot.org/core/author"Loyant R."xsd:string
http://purl.uniprot.org/citations/27538435http://purl.uniprot.org/core/author"Loyant R."xsd:string
http://purl.uniprot.org/citations/27538435http://purl.uniprot.org/core/author"Munitic I."xsd:string
http://purl.uniprot.org/citations/27538435http://purl.uniprot.org/core/author"Munitic I."xsd:string
http://purl.uniprot.org/citations/27538435http://purl.uniprot.org/core/author"Pourcelot M."xsd:string
http://purl.uniprot.org/citations/27538435http://purl.uniprot.org/core/author"Pourcelot M."xsd:string
http://purl.uniprot.org/citations/27538435http://purl.uniprot.org/core/author"Silva Da Costa L."xsd:string
http://purl.uniprot.org/citations/27538435http://purl.uniprot.org/core/author"Silva Da Costa L."xsd:string
http://purl.uniprot.org/citations/27538435http://purl.uniprot.org/core/author"Zemirli N."xsd:string
http://purl.uniprot.org/citations/27538435http://purl.uniprot.org/core/author"Zemirli N."xsd:string
http://purl.uniprot.org/citations/27538435http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/27538435http://purl.uniprot.org/core/date"2016"xsd:gYear
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