Mst1 shuts off cytosolic antiviral defense through IRF3 phosphorylation
In: Genes & Development, Jg. 30 (2016-05-01), Heft 9
academicJournal
- 1086 - 1100
Zugriff:
Cytosolic RNA/DNA sensing elicits primary defense against viral pathogens. Interferon regulatory factor 3 (IRF3), a key signal mediator/transcriptional factor of the antiviral-sensing pathway, is indispensible for interferon production and antiviral defense. However, how the status of IRF3 activation is controlled remains elusive. Through a functional screen of the human kinome, we found that mammalian sterile 20-like kinase 1 (Mst1), but not Mst2, profoundly inhibited cytosolic nucleic acid sensing. Mst1 associated with IRF3 and directly phosphorylated IRF3 at Thr75 and Thr253. This Mst1-mediated phosphorylation abolished activated IRF3 homodimerization, its occupancy on chromatin, and subsequent IRF3-mediated transcriptional responses. In addition, Mst1 also impeded virus-induced activation of TANK-binding kinase 1 (TBK1), further attenuating IRF3 activation. As a result, Mst1 depletion or ablation enabled an enhanced antiviral response and defense in cells and mice. Therefore, the identification of Mst1 as a novel physiological negative regulator of IRF3 activation provides mechanistic insights into innate antiviral defense and potential antiviral prevention strategies.
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Mst1 shuts off cytosolic antiviral defense through IRF3 phosphorylation
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Autor/in / Beteiligte Person: | Meng, Fansen ; Zhou, Ruyuan ; Wu, Shiying ; Zhang, Qian ; Jin, Qiuheng ; Zhou, Yao ; Plouffe, Steven W ; Liu, Shengduo ; Song, Hai ; Xia, Zongping ; Zhao, Bin ; Ye, Sheng ; Feng, Xin-Hua ; Guan, Kun-Liang ; Zou, Jian ; Xu, Pinglong |
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Zeitschrift: | Genes & Development, Jg. 30 (2016-05-01), Heft 9 |
Veröffentlichung: | eScholarship, University of California, 2016 |
Medientyp: | academicJournal |
Umfang: | 1086 - 1100 |
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