YAP antagonizes innate antiviral immunity and is targeted for lysosomal degradation through IKKɛ-mediated phosphorylation - PubMed (original) (raw)
. 2017 Jul;18(7):733-743.
doi: 10.1038/ni.3744. Epub 2017 May 8.
Feng Xie 2, Feng Chu 1, Zhengkui Zhang 2, Bing Yang 3, Tong Dai 1, Liang Gao 1, Lin Wang 1, Li Ling 1, Junling Jia 2, Hans van Dam 4, Jin Jin 2, Long Zhang 2, Fangfang Zhou 1
Affiliations
- PMID: 28481329
- DOI: 10.1038/ni.3744
YAP antagonizes innate antiviral immunity and is targeted for lysosomal degradation through IKKɛ-mediated phosphorylation
Shuai Wang et al. Nat Immunol. 2017 Jul.
Erratum in
- Corrigendum: YAP antagonizes innate antiviral immunity and is targeted for lysosomal degradation through IKKɛ-mediated phosphorylation.
Wang S, Xie F, Chu F, Zhang Z, Yang B, Dai T, Gao L, Wang L, Ling L, Jia J, van Dam H, Jin J, Zhang L, Zhou F. Wang S, et al. Nat Immunol. 2017 Oct 18;18(11):1270. doi: 10.1038/ni1117-1270d. Nat Immunol. 2017. PMID: 29044228
Abstract
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 IKKɛ 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.
Comment in
- Balancing anti-viral innate immunity and immune homeostasis.
Mishra S, Kumar H. Mishra S, et al. Cell Mol Immunol. 2018 Apr;15(4):408-410. doi: 10.1038/cmi.2017.98. Epub 2017 Oct 2. Cell Mol Immunol. 2018. PMID: 28967876 Free PMC article. No abstract available. - Relief of YAP-mediated inhibition by IKKɛ promotes innate antiviral immunity.
Kim N, Park YY, Joo CH, Kim HS. Kim N, et al. Cell Mol Immunol. 2018 Jun;15(6):642-644. doi: 10.1038/cmi.2017.97. Epub 2017 Oct 23. Cell Mol Immunol. 2018. PMID: 29057972 Free PMC article. No abstract available.
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