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
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
PubMed ID: 28346439
View in: Pubmed Google Scholar
Download Curated Data For This Publication
208378
Switch View:
- Interactions 10