Negative regulation of MDA5- but not RIG-I-mediated innate antiviral signaling by the dihydroxyacetone kinase.
Proc Natl Acad Sci U S A
; 104(28): 11706-11, 2007 Jul 10.
Article
en En
| MEDLINE
| ID: mdl-17600090
Viral infection leads to activation of the transcription factors interferon regulatory factor-3 and NF-kappaB, which collaborate to induce type I IFNs. The RNA helicase proteins RIG-I and MDA5 were recently identified as two cytoplasmic viral RNA sensors that recognize different species of viral RNAs produced during viral replication. In this study, we identified DAK, a functionally unknown dihydroacetone kinase, as a specific MDA5-interacting protein. DAK was associated with MDA5, but not RIG-I, under physiological conditions. Overexpression of DAK inhibited MDA5- but not RIG-I- or TLR3-mediated IFN-beta induction. Overexpression of DAK also inhibited cytoplasmic dsRNA and SeV-induced activation of the IFN-beta promoter, whereas knockdown of endogenous DAK by RNAi activated the IFN-beta promoter, and increased cytoplasmic dsRNA- or SeV-triggered activation of the IFN-beta promoter. In addition, overexpression of DAK inhibited MDA5- but not RIG-I-mediated antiviral activity, whereas DAK RNAi increased cytoplasmic dsRNA-triggered antiviral activity. These findings suggest that DAK is a physiological suppressor of MDA5 and specifically inhibits MDA5- but not RIG-I-mediated innate antiviral signaling.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Fosfotransferasas (Aceptor de Grupo Alcohol)
/
Virus de la Estomatitis Vesicular Indiana
/
Virus Sendai
/
Inactivación de Virus
/
ARN Helicasas DEAD-box
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2007
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos