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Nat Cell Biol. 2017 Apr;19(4):362-374. doi: 10.1038/ncb3496. Epub 2017 Mar 27.

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

Author information

1
Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China.
2
Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, California 92093, USA.
3
Department of Cardiology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
4
The Key Laboratory of Stem Cell Biology, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
5
Eye Center of the Second Affiliated Hospital School of Medicine, Institutes of Translational Medicine, Zhejiang University, Hangzhou 310058, China.
6
Michael E. DeBakey Department of Surgery and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.

Abstract

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.

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PMID:
28346439
PMCID:
PMC5398908
DOI:
10.1038/ncb3496
[Indexed for MEDLINE]
Free PMC Article

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