PUBLICATION
Hippo signalling governs cytosolic nucleic acid sensing through YAP/TAZ-mediated TBK1 blockade
- Authors
- Zhang, Q., Meng, F., Chen, S., Plouffe, S.W., Wu, S., Liu, S., Li, X., Zhou, R., Wang, J., Zhao, B., Liu, J., Qin, J., Zou, J., Feng, X.H., Guan, K.L., Xu, P.
- ID
- ZDB-PUB-170328-1
- Date
- 2017
- Source
- Nature cell biology 19(4): 362-374 (Journal)
- Registered Authors
- Zou, Jian
- Keywords
- Cell signalling, HIPPO signalling, Zebrafish
- MeSH Terms
-
- Phosphoproteins/chemistry
- Phosphoproteins/metabolism*
- Tumor Suppressor Proteins/metabolism
- RNA/metabolism
- Protein Serine-Threonine Kinases/metabolism*
- Interferon Regulatory Factor-3/genetics
- Interferon Regulatory Factor-3/metabolism
- Cytosol/metabolism*
- Animals
- Mice, Inbred C57BL
- Protein Binding/drug effects
- Ubiquitination/drug effects
- Transcription, Genetic/drug effects
- Transcriptional Activation/genetics
- Nucleic Acids/metabolism*
- Signal Transduction*
- Gene Expression Regulation/drug effects
- Transcription Factors/metabolism*
- Adaptor Proteins, Signal Transducing/chemistry
- Adaptor Proteins, Signal Transducing/metabolism*
- HEK293 Cells
- Fluorescent Antibody Technique
- Zebrafish/embryology
- Lysine/metabolism
- Antiviral Agents/pharmacology
- Doxorubicin/pharmacology
- Humans
- Protein Domains
- DNA/metabolism
- PubMed
- 28346439 Full text @ Nat. Cell Biol.
Citation
Zhang, Q., Meng, F., Chen, S., Plouffe, S.W., Wu, S., Liu, S., Li, X., Zhou, R., Wang, J., Zhao, B., Liu, J., Qin, J., Zou, J., Feng, X.H., Guan, K.L., Xu, P. (2017) Hippo signalling governs cytosolic nucleic acid sensing through YAP/TAZ-mediated TBK1 blockade. Nature cell biology. 19(4):362-374.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping