Hippo signalling governs cytosolic nucleic acid sensing through YAP/TAZ-mediated TBK1 blockade

被引：175

作者：

Zhang, Qian ^{[1
,2
]}

Meng, Fansen ^{[1
,2
]}

Chen, Shasha ^{[1
,2
]}

Plouffe, Steven W. ^{[3
,4
]}

Wu, Shiying ^{[1
,2
]}

Liu, Shengduo ^{[1
,2
]}

Li, Xinran ^{[1
,2
]}

Zhou, Ruyuan ^{[1
,2
]}

Wang, Junxian ^{[1
,2
]}

Zhao, Bin ^{[1
,2
]}

Liu, Jianming ^{[5
]}

Qin, Jun ^{[6
]}

Zou, Jian ^{[7
]}

Feng, Xin-Hua ^{[1
,2
,8
,9
]}

Guan, Kun-Liang ^{[3
,4
]}

Xu, Pinglong ^{[1
,2
]}

机构：

[1] Zhejiang Univ, Inst Life Sci, Hangzhou 310058, Zhejiang, Peoples R China

[2] Zhejiang Univ, Innovat Ctr Cell Signaling Network, Hangzhou 310058, Zhejiang, Peoples R China

[3] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA

[4] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA

[5] Harvard Med Sch, Boston Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA

[6] Chinese Acad Sci, Key Lab Stem Cell Biol, Chinese Acad Sci Ctr Excellence Mol Cell Sci, Inst Hlth Sci,Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China

[7] Zhejiang Univ, Inst Translat Med, Affiliated Hosp 2, Eye Ctr,Sch Med, Hangzhou 310058, Zhejiang, Peoples R China

[8] Baylor Coll Med, Michael E DeBakey Dept Surg, Houston, TX 77030 USA

[9] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

来源：

NATURE CELL BIOLOGY | 2017年 / 19卷 / 04期

基金：

中央高校基本科研业务费专项资金资助;

关键词：

ORGAN SIZE CONTROL; GMP-AMP SYNTHASE; BINDING KINASE 1; NF-KAPPA-B; CELL SELF-RENEWAL; INNATE IMMUNITY; PROMOTES APOPTOSIS; YAP PATHWAY; IKK-EPSILON; RIG-I;

D O I：

10.1038/ncb3496

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The Hippo pathway senses cellular conditions and regulates YAP/TAZ to control cellular and tissue homeostasis, while TBK1 is central for cytosolic nucleic acid sensing and antiviral defence. The correlation between cellular nutrient/physical status and host antiviral defence is interesting but not well understood. Here we find that YAP/TAZ act as natural inhibitors of TBK1 and are vital for antiviral physiology. Independent of transcriptional regulation and through the transactivation domain, YAP/TAZ associate directly with TBK1 and abolish virus-induced TBK1 activation, by preventing TBK1 Lys63-linked ubiquitylation and the binding of adaptors/substrates. Accordingly, YAP/TAZ deletion/depletion or cellular conditions inactivating YAP/TAZ through Lats1/2 kinases relieve TBK1 suppression and boost antiviral responses, whereas expression of the transcriptionally inactive YAP dampens cytosolic RNA/DNA sensing and weakens the antiviral defence in cells and zebrafish. Thus, we describe a function of YAP/TAZ and the Hippo pathway in innate immunity, by linking cellular nutrient/physical status to antiviral host defence.

引用

页码：362 / +

页数：25

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