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High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes
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Transducción de la señal dependiente de la acetilación para el receptor de interferón tipo I
Xiaoli Tang1, Jin-Song Gao, Ying-jie Guan
1Department of Surgery, Brown University Medical School, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA.
Cell
|October 10, 2007
Resumen
La señalización de los receptores de citoquinas implica la acetilación. La proteína de unión al CREB (CBP) acetila el receptor alfa del interferón 2 (IFNAR2), lo que permite la regulación del gen antiviral a través del complejo ISGF3.
Área de la Ciencia:
- La señalización celular de las células.
- Biología molecular La biología molecular.
- Inmunología Inmunología.
Sus antecedentes:
- Los receptores activados por citocinas inician la señalización mediante el reclutamiento de las quinasas.
- La fosforilación de los receptores permite el acoplamiento de los factores portadores del dominio SH2.
Objetivo del estudio:
- Para investigar el papel de la proteína de unión al CREB (CBP) en la señalización del interferón tipo 1 (IFNα).
- Aclarar el mecanismo de reclutamiento del factor regulador del interferón 9 (IRF9) y la formación del complejo ISGF3.
Principales métodos:
- Pruebas de coinmunoprecipitación para estudiar las interacciones de las proteínas.
- Ensayos de acetilación in vitro para determinar la actividad de la CBP.
- Mutagénesis dirigida al sitio para identificar residuos críticos.
Principales resultados:
- Los receptores IFNα reclutan CBP citoplasmático tras la estimulación de IFNα.
- CBP acetila IFNAR2 en Lys399, creando un sitio de acoplamiento para IRF9.9.
- La acetilación de IRF9 y STAT2 dentro de sus dominios de unión al ADN es crucial para la activación del complejo ISGF3 y la expresión génica antiviral.
Conclusiones:
- La acetilación, mediada por la CBP, es un mecanismo regulador crítico en la transducción de la señal del receptor de citoquinas.
- Esta vía pone de relieve un nuevo papel para la acetilación en la inmunidad antiviral.
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