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Pinglong Xu Lab, Nature Cell Biology: Hippo signalling governs cytosolic nucleic acid sensing through YAP/TAZ-mediated TBK1 blockade.


On March 27th 2017, Pinglong Xu laboratory published the research article in Nature Cell Biology entitled “Hippo signalling governs cytosolic nucleic acid sensing through YAP/TAZ-mediated TBK1 blockade”, which describes an interesting regulation of cellular nutrient/physical stresses to antiviral host defense through Hippo-YAP signaling.

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 defense. The correlation between cellular nutrient/physical status and host antiviral defense is interesting but not well understood. Here Xu laboratory finds that YAP/TAZ act as natural inhibitors of TBK1 and are vital for antiviral physiology. Independent of transcriptional regulation and through transactivation domain, YAP/TAZ associate directly with TBK1 and abolish virus-induced TBK1 activation, by preventing TBK1 K63-linked ubiquitination and adaptors/substrates binding. 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 defense in cells and zebrafish. Thus, Xu laboratory describes a function of YAP/TAZ and the Hippo pathway in innate immunity, by linking cellular nutrient/physical status to antiviral host defense.

Ph.D. candidate Qian Zhang and Fansen Meng in Xu laboratory are the first authors, graduate student Shasha Chen is the second author, and Dr. Pinglong Xu is the corresponding author of this research article. This study was collaborated by Drs. Kun-Liang Guan, Xin-Hua Feng, Jian Zou and other colleagues, sponsored by the NSFC Project, the MOST 973 plan, and the National 1000 Young Talents Program, and accomplished in Life Sciences Institute (LSI) and Innovation Center of Cell Signaling Network at Zhejiang University. Nature Cell Biology is a sub-issue of Nature and the top tier journal in cell biology, with an IF of 18.699.

Mechanism for nutrient/physical stresses-mediated regulation antiviral host defense
through interplay between Hippo-YAP signaling and cytosolic nucleic acid sensing.