YAP antagonizes innate antiviral immunity and is targeted for lysosomal degradation through IKKÉ-mediated phosphorylation.
Nat Immunol
; 18(7): 733-743, 2017 Jul.
Article
em En
| MEDLINE
| ID: mdl-28481329
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 IKKÉ 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
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Infecções por Rhabdoviridae
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Proteínas Adaptadoras de Transdução de Sinal
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Quinase I-kappa B
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Fibroblastos
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Imunidade Inata
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Lisossomos
/
Macrófagos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Nat Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
China