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

共 69 条

[61] Innate Antiviral Host Defense Attenuates TGF-β Function through IRF3-Mediated Suppression of Smad Signaling [J].

Xu, Pinglong ;

Bailey-Bucktrout, Samantha ;

Xi, Ying ;

Xu, Daqi ;

Du, Dan ;

Zhang, Qian ;

Xiang, Weiwen ;

Liu, Jianming ;

Melton, Andrew ;

Sheppard, Dean ;

Chapman, Harold A. ;

Bluestone, Jeffrey A. ;

Derynck, Rik .

MOLECULAR CELL, 2014, 56 (06) :723-737

[62] The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses [J].

Yoneyama, M ;

Kikuchi, M ;

Natsukawa, T ;

Shinobu, N ;

Imaizumi, T ;

Miyagishi, M ;

Taira, K ;

Akira, S ;

Fujita, T .

NATURE IMMUNOLOGY, 2004, 5 (07) :730-737

[63] Hippo Pathway in Organ Size Control, Tissue Homeostasis, and Cancer [J].

Yu, Fa-Xing ;

Zhao, Bin ;

Guan, Kun-Liang .

CELL, 2015, 163 (04) :811-828

[64] Protein kinase A activates the Hippo pathway to modulate cell proliferation and differentiation [J].

Yu, Fa-Xing ;

Zhang, Yifan ;

Park, Hyun Woo ;

Jewell, Jenna L. ;

Chen, Qian ;

Deng, Yaoting ;

Pan, Duojia ;

Taylor, Susan S. ;

Lai, Zhi-Chun ;

Guan, Kun-Liang .

GENES & DEVELOPMENT, 2013, 27 (11) :1223-1232

[65] Regulation of the Hippo-YAP Pathway by G-Protein-Coupled Receptor Signaling [J].

Yu, Fa-Xing ;

Zhao, Bin ;

Panupinthu, Nattapon ;

Jewell, Jenna L. ;

Lian, Ian ;

Wang, Lloyd H. ;

Zhao, Jiagang ;

Yuan, Haixin ;

Tumaneng, Karen ;

Li, Hairi ;

Fu, Xiang-Dong ;

Mills, Gordon B. ;

Guan, Kun-Liang .

CELL, 2012, 150 (04) :780-791

[66] TEAD mediates YAP-dependent gene induction and growth control [J].

Zhao, Bin ;

Ye, Xin ;

Yu, Jindan ;

Li, Li ;

Li, Weiquan ;

Li, Siming ;

Yu, Jianjun ;

Lin, Jiandie D. ;

Wang, Cun-Yu ;

Chinnaiyan, Arul M. ;

Lai, Zhi-Chun ;

Guan, Kun-Liang .

GENES & DEVELOPMENT, 2008, 22 (14) :1962-1971

[67] Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control [J].

Zhao, Bin ;

Wei, Xiaomu ;

Li, Weiquan ;

Udan, Ryan S. ;

Yang, Qian ;

Kim, Joungmok ;

Xie, Joe ;

Ikenoue, Tsuneo ;

Yu, Jindan ;

Li, Li ;

Zheng, Pan ;

Ye, Keqiang ;

Chinnaiyan, Arul ;

Halder, Georg ;

Lai, Zhi-Chun ;

Guan, Kun-Liang .

GENES & DEVELOPMENT, 2007, 21 (21) :2747-2761

[68] The Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal [J].

Zhao, Bin ;

Tumaneng, Karen ;

Guan, Kun-Liang .

NATURE CELL BIOLOGY, 2011, 13 (08) :877-883

[69] The Hippo-YAP pathway in organ size control and tumorigenesis: an updated version [J].

Zhao, Bin ;

Li, Li ;

Lei, Qunying ;

Guan, Kun-Liang .

GENES & DEVELOPMENT, 2010, 24 (09) :862-874

← 1 2 3 4 5 6 7 →