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
  • Adaptor Proteins, Signal Transducing/chemistry
  • Adaptor Proteins, Signal Transducing/metabolism*
  • Animals
  • Antiviral Agents/pharmacology
  • Cytosol/metabolism*
  • DNA/metabolism
  • Doxorubicin/pharmacology
  • Fluorescent Antibody Technique
  • Gene Expression Regulation/drug effects
  • HEK293 Cells
  • Humans
  • Interferon Regulatory Factor-3/genetics
  • Interferon Regulatory Factor-3/metabolism
  • Lysine/metabolism
  • Mice, Inbred C57BL
  • Nucleic Acids/metabolism*
  • Phosphoproteins/chemistry
  • Phosphoproteins/metabolism*
  • Protein Binding/drug effects
  • Protein Domains
  • Protein Serine-Threonine Kinases/metabolism*
  • RNA/metabolism
  • Signal Transduction*
  • Transcription Factors/metabolism*
  • Transcription, Genetic/drug effects
  • Transcriptional Activation/genetics
  • Tumor Suppressor Proteins/metabolism
  • Ubiquitination/drug effects
  • Zebrafish/embryology
PubMed
28346439 Full text @ Nat. Cell Biol.
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
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping