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Asociación funcional de Nmi con Stat5 y Stat1 en la señalización mediada por IL-2 y IFNgamma

M Zhu¹, S John, M Berg

¹Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1674, USA.

|February 16, 1999

Resumen

La proteína interactiva del receptor nuclear (Nmi) mejora la transcripción mediada por STAT aumentando el reclutamiento de proteínas coactivadoras. Esta proteína potencia la transcripción en respuesta a las citoquinas IL-2 y IFNgamma.

Área de la Ciencia:

Biología Molecular Biología Molecular
La señalización celular de las células.
Interacciones de las proteínas.

Sus antecedentes:

Los transductores de señales y las proteínas activadoras de la transcripción (STAT) son mediadores clave de la señalización de citoquinas.
La función de la proteína que interactúa con los receptores nucleares (Nmi) es en gran medida desconocida.
Nmi ha sido previamente identificado como un interactor N-Myc.

Objetivo del estudio:

Para identificar nuevas proteínas que interactúan con STAT.
Investigar el papel de Nmi en la regulación transcripcional mediada por STAT.
Para aclarar el mecanismo por el cual Nmi influye en la actividad STAT.

Principales métodos:

Cribado de dos híbridos de levadura utilizando la región en espiral de Stat5b como cebo.
Los ensayos de coinmunoprecipitación confirman las interacciones de las proteínas.
Los ensayos del gen reportero miden la actividad transcripcional en respuesta a citoquinas como IL-2 e IFNgamma.

Principales resultados:

Nmi fue identificado como una proteína que interactúa con Stat5b.
Nmi interactúa con múltiples proteínas STAT, excluyendo Stat2.
Nmi potencia la IL-2 y la transcripción STAT-mediada inducida por IFNgamma.
Nmi mejora el reclutamiento de coactivadores CBP/p300 para Stat1 y Stat5.

Conclusiones:

Nmi actúa como un regulador positivo de la transcripción dependiente de STAT.
Nmi funciona facilitando la asociación de STAT con las proteínas coactivadoras como CBP/p300.
El papel de Nmi en el aumento del reclutamiento de coactivadores destaca su importancia en las vías de señalización de citoquinas.

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