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

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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Antiviral Agents, Cytosol, DNA, Doxorubicin, Fluorescent Antibody Technique, Gene Expression Regulation, HEK293 Cells, Humans, Interferon Regulatory Factor-3, Lysine, Mice, Inbred C57BL, Nucleic Acids, Phosphoproteins, Protein Binding, Protein Domains, Protein-Serine-Threonine Kinases, RNA, Signal Transduction, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Tumor Suppressor Proteins, Ubiquitination, Zebrafish
Nat. Cell Biol.
Date: Dec. 01, 2016
Download Curated Data For This Publication
208378
Switch View:
  • Interactions 10