Ndfip1 negatively regulates RIG-I-dependent immune signaling by enhancing E3 ligase Smurf1-mediated MAVS degradation.
J Immunol
; 189(11): 5304-13, 2012 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-23087404
ABSTRACT
Ndfip1 functions as both a recruiter and an activator of multiple HECT domain E3 ubiquitin ligases of the Nedd4 family. In this study, we demonstrate that Ndfip1 is involved in the ubiquitin-mediated degradation of mitochondrial antiviral signaling (MAVS), which is a key adaptor protein in RIG-I-like receptor-mediated immune signaling. We found that overexpression of Ndfip1 severely impaired MAVS and Sendai virus-mediated activation of IFN-stimulated response element, NF-κB, IFN-ß promoter, and polyinosinic-polycytidylic acid or influenza virus RNA-stimulated IRF-3 phosphorylation, as well as the transcription of IFN-ß. This functional interaction was confirmed by knockdown of Ndfip1, which facilitated MAVS-mediated downstream signaling and elevated MAVS protein levels. Further analysis indicated that Ndfip1 enhances both self-ubiquitination of HECT domain-containing E3 ubiquitin ligase Smurf1 and its interaction with MAVS, and eventually promotes MAVS degradation. In addition, the activation of IFN-ß by MAVS, influenza virus RNA, polyinosinic-polycytidylic acid, and Sendai virus was enhanced in Ndfip1 knockdown cells. These results reveal that Ndfip1 is a potent inhibitor of MAVS-mediated antiviral response.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA Viral
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Proteínas de Transporte
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Ubiquitina-Proteína Ligases
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Proteínas Adaptadoras de Transdução de Sinal
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RNA Helicases DEAD-box
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Proteínas de Membrana
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
China