| First Author | Wang S | Year | 2017 |
| Journal | Nat Immunol | Volume | 18 |
| Issue | 7 | Pages | 733-743 |
| PubMed ID | 28481329 | Mgi Jnum | J:259467 |
| Mgi Id | MGI:6143886 | Doi | 10.1038/ni.3744 |
| Citation | Wang S, et al. (2017) YAP antagonizes innate antiviral immunity and is targeted for lysosomal degradation through IKKvarepsilon-mediated phosphorylation. Nat Immunol 18(7):733-743 |
| abstractText | 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 IKKvarepsilon 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. |
