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Se requiere una vía dependiente de JNK para la apoptosis inducida por TNFalpha
Yibin Deng1, Xiaoyang Ren, Lin Yang
1Huffington Center on Aging and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 70030, USA.
Cell
|October 9, 2003
Resumen
La señalización del factor de necrosis tumoral (TNFalpha) activa el JNK, que divide el Bid. Esto libera Smac/DIABLO, aliviando la inhibición y permitiendo la activación de la caspasa 8 para la apoptosis.
Área de la Ciencia:
- Las vías de señalización celular.
- Apoptosis y los mecanismos de muerte celular.
- Biología molecular de la señalización de TNFalpha.
Sus antecedentes:
- La señalización del receptor del factor de necrosis tumoral alfa (TNFalpha) activa múltiples efectores aguas abajo, incluidos la caspasa 8, NF-kappaB y JNK.
- Si bien la caspasa 8 es esencial para la apoptosis inducida por TNFalpha y la NF-kappaB inhibe la muerte celular, el papel de la JNK en esta vía sigue sin estar claro.
Objetivo del estudio:
- Para dilucidar la función precisa de la activación de JNK en la apoptosis mediada por TNFalpha.
- Para definir la vía secuencial que une la activación de la JNK a la escisión de la caspasa 8 y la muerte celular.
Principales métodos:
- Investigó el papel de JNK, Bid y Smac/DIABLO en la señalización de TNFalpha utilizando técnicas de biología molecular.
- Se analizó la escisión de la caspasa 8, la generación de productos de la escisión de Bid (jBid) y la liberación mitocondrial de proteínas.
- Examinó la interrupción del complejo TRAF2-cIAP1 por Smac/DIABLO.
Principales resultados:
- La apoptosis mediada por TNFalpha requiere una vía secuencial que involucra a JNK, Bid y Smac/DIABLO.
- La activación de JNK conduce a la escisión caspase 8-independiente de Bid, generando jBid.
- La translocación de jBid a las mitocondrias da como resultado la liberación de Smac/DIABLO, que interrumpe el complejo TRAF2-cIAP1.
Conclusiones:
- La vía JNK es esencial para aliviar la inhibición mediada por TRAF2-cIAP1 de la activación de la caspasa 8 y la apoptosis.
- Este estudio revela un nuevo mecanismo de interconexión entre las vías intrínsecas y extrínsecas de muerte celular.
- Los hallazgos proporcionan nuevos conocimientos sobre la regulación de la muerte celular inducida por TNFalpha.
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