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Cell Res. 2016 May;26(5):613-28. doi: 10.1038/cr.2016.27. Epub 2016 Feb 26.

TRIM9 short isoform preferentially promotes DNA and RNA virus-induced production of type I interferon by recruiting GSK3β to TBK1.

Qin Y1, Liu Q1, Tian S1, Xie W2, Cui J1,3, Wang RF4,5,6.

Author information

1
Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China.
2
Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
3
Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
4
Houston Methodist Research Institute, Houston, TX 77030, USA.
5
Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA.
6
Institute of Biosciences and Technology, College of Medicine, Texas A & M University, Houston, TX 77030, USA.

Abstract

Type I interferon (IFN) is an important component of antiviral innate immune signaling mediated by viral DNA and RNA recognition by the DNA sensor cGAS and RNA sensors RIG-I and MDA5. Activation of these DNA and RNA sensors leads to the recruitment of STING and MAVS, respectively, and converges on TANK-binding kinase 1 (TBK1) signaling for subsequent phosphorylation of IFN regulatory factor 3 (IRF3). However, the mechanisms that control TBK1 activation are still poorly defined. Here, we identify tripartite motif 9 short isoform (TRIM9s) as a positive regulator in type I IFN signaling. Upon viral infection, TRIM9s undergoes Lys-63-linked auto-polyubiquitination and serves as a platform to bridge GSK3β to TBK1, leading to the activation of IRF3 signaling. Interestingly, we found that TRIM9s selectively inhibits the production of pro-inflammatory cytokines, but enhances the expression of type I IFNs as well as IFN-stimulated genes, in response to viral infection. Our findings reveal novel dual functions of TRIM9s in antiviral immunity, which serve to balance pro-inflammatory response and production of type I IFNs.

PMID:
26915459
PMCID:
PMC4856760
DOI:
10.1038/cr.2016.27
[Indexed for MEDLINE]
Free PMC Article

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