Publication: Hippo signaling governs cytosolic nucleic acid sensing through YAP/TAZ-mediated TBK1 blockade
Open/View Files
Date
2017
Published Version
Journal Title
Journal ISSN
Volume Title
Publisher
The Harvard community has made this article openly available. Please share how this access benefits you.
Citation
Zhang, Q., F. Meng, S. Chen, S. W. Plouffe, S. Wu, S. Liu, X. Li, et al. 2017. “Hippo signaling governs cytosolic nucleic acid sensing through YAP/TAZ-mediated TBK1 blockade.” Nature cell biology 19 (4): 362-374. doi:10.1038/ncb3496. http://dx.doi.org/10.1038/ncb3496.
Research Data
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 defense. The correlation between cellular nutrient/physical status and host antiviral defense 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 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, we describe a function of YAP/TAZ and the Hippo pathway in innate immunity, by linking cellular nutrient/physical status to antiviral host defense.
Description
Other Available Sources
Keywords
Hippo pathway, YAP/TAZ, TBK1, antiviral response, host defense
Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material (LAA), as set forth at Terms of Service