Journal
NATURE IMMUNOLOGY
Volume 18, Issue 7, Pages 733-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3744
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Funding
- Ministry of Science and Technology of China [2016YFA0502500]
- Chinese National Natural Science Funds [31571460, 31471315, 31671457]
- PCSIRT [IRT1075]
- Jiangsu National Science Foundation [BK20150354]
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The transcription regulator YAP controls organ size by regulating cell growth, proliferation and apoptosis. However, whether YAP has a role in innate antiviral immunity is largely unknown. Here we found that YAP negatively regulated an antiviral immune response. YAP deficiency resulted in enhanced innate immunity, a diminished viral load, and morbidity in vivo. YAP blocked dimerization of the transcription factor IRF3 and impeded translocation of IRF3 to the nucleus after viral infection. Notably, virus-activated kinase IKK epsilon phosphorylated YAP at Ser403 and thereby triggered degradation of YAP in lysosomes and, consequently, relief of YAP-mediated inhibition of the cellular antiviral response. These findings not only establish YAP as a modulator of the activation of IRF3 but also identify a previously unknown regulatory mechanism independent of the kinases Hippo and LATS via which YAP is controlled by the innate immune pathway.
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