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La activación de la kinasa reguladora de la señal de la apoptosis 1 (ASK1) por la proteína adaptadora Daxxxx
H Y Chang1, H Nishitoh, X Yang
1Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02138, USA.
Science (New York, N.Y.)
|September 22, 1998
Resumen
La vía del receptor de muerte Fas activa la señalización de la kinasa Jun NH2-terminal (JNK) a través de la proteína Daxx, que interactúa y activa la kinasa ASK1, promoviendo la apoptosis.
Área de la Ciencia:
- Las vías de señalización celular.
- Apoptosis y muerte celular.
- Biología molecular La biología molecular.
Sus antecedentes:
- El receptor de la muerte Fas inicia la apoptosis celular.
- Daxx es una proteína asociada con el receptor Fas.
- La activación de la vía Jun NH2-terminal kinase (JNK) es crucial en la apoptosis.
Objetivo del estudio:
- Para aclarar el papel de Daxx en la activación de JNK mediada por Fas.
- Para identificar la interacción entre Daxx y ASK1 en la vía de señalización Fas.
- Para entender cómo Daxx regula la actividad de la kinasa ASK1.
Principales métodos:
- Sobreexpresión de mutantes ASK1 de tipo silvestre y con deficiencia de quinasa.
- Análisis de la apoptosis inducida por Fas y Daxx.
- Evaluación de la activación de la JNK.
- Co-inmunoprecipitación para estudiar las interacciones de las proteínas.
Principales resultados:
- Daxx activa la kinasa kinasa de la JNK ASK1.1, también conocida como kinasa de la JNK.
- La sobreexpresión de un mutante ASK1 con deficiencia de kinasa inhibe la apoptosis inducida por Fas y Daxx y la activación del JNK.
- La activación de Fas promueve la interacción de Daxx con ASK1.1.
- La unión de Daxx alivia la inhibición intramolecular de ASK1, activando su actividad de la quinasa.
Conclusiones:
- La interacción Daxx-ASK1 es esencial para la activación del JNK inducida por Fas y la apoptosis.
- Este estudio define una cascada de señalización desde el receptor Fas hasta la activación de la vía JNK.
- Los hallazgos revelan un mecanismo para regular la actividad de la ASK1 quinasa a través de proteínas asociadas al receptor.
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