ER Adaptor SCAP Translocates and Recruits IRF3 to Perinuclear Microsome Induced by Cytosolic Microbial DNAs: e1005462

Stimulator of interferon genes (STING, also known as MITA, ERIS or MPYS) induces the activation of TBK1 kinase and IRF3 transcription factor, upon sensing of microbial DNAs. How IRF3 is recruited onto the STING signalosome remains unknown. We report here that silencing of the ER adaptor SCAP markedl...

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Bibliographic Details
Published in:PLoS pathogens 2016-02, Vol.12 (2)
Main Authors: Chen, Wei, Li, Senlin, Yu, Huansha, Liu, Xing, Huang, Lulu, Wang, Qiang, Liu, Heng, Cui, Ye, Tang, Yijun, Zhang, Peng, Wang, Chen
Format: Article
Language:English
Subjects:
Cytokines
Deoxyribonucleic acid
DNA
Experiments
Gene expression
Herpesviridae
Homeostasis
Immunoglobulins
Infections
Kinases
Microscopy
Proteins
RNA polymerase
Science
Sensors
Signal transduction
Transcription factors
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Summary:Stimulator of interferon genes (STING, also known as MITA, ERIS or MPYS) induces the activation of TBK1 kinase and IRF3 transcription factor, upon sensing of microbial DNAs. How IRF3 is recruited onto the STING signalosome remains unknown. We report here that silencing of the ER adaptor SCAP markedly impairs the IRF3-responsive gene expression induced by STING. Scap knockdown mice are more susceptible to HSV-1 infection. Interestingly, SCAP translocates from ER, via Golgi, to perinuclear microsome in a STING-dependent manner. Mechanistically, the N-terminal transmembrane domain of SCAP interacts with STING, and the C-terminal cytosolic domain of SCAP binds to IRF3, thus recruiting IRF3 onto STING signalosome. Mis-localization of SCAP abolishes its antiviral function. Collectively, this study characterizes SCAP as an essential adaptor in the STING signaling pathway, uncovering a critical missing link in DNAs-triggered host antiviral responses.
ISSN:1553-7366
1553-7374
DOI:10.1371/journal.ppat.1005462