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La activación de mTORC2 por asociación con el ribosoma
Vittoria Zinzalla1, Daniele Stracka, Wolfgang Oppliger
1Biozentrum, University of Basel, CH-4056 Basel, Switzerland.
Cell
|March 8, 2011
Resumen
Los ribosomas, no la síntesis de proteínas, son esenciales para la señalización del complejo de rapamicina 2 (mTORC2) en mamíferos. Esta interacción conservada del mTORC2-ribosoma es crucial para el crecimiento celular y la progresión del cáncer.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- La bioquímica es la bioquímica.
Sus antecedentes:
- El objetivo de la vía de la rapamicina (TOR) es un regulador central del crecimiento celular y el metabolismo.
- El complejo TOR de mamíferos 2 (mTORC2) controla las quinasas AGC y está involucrado en enfermedades como el cáncer y la diabetes.
- Los reguladores aguas arriba de la actividad mTORC2 siguen siendo incompletamente entendidos.
Objetivo del estudio:
- Para aclarar los mecanismos de regulación aguas arriba de la señalización mTORC2.
- Para investigar el papel de los ribosomas y la síntesis de proteínas en la activación de mTORC2.
- Para determinar la relevancia fisiológica de la regulación de mTORC2 en las células normales y cancerosas.
Principales métodos:
- Cribado genético en levaduras.
- Estudios en líneas celulares de mamíferos, incluidas las células de melanoma y cáncer de colon.
- Análisis de la asociación mTORC2-ribosoma y la señalización de PI3K.
Principales resultados:
- Los ribosomas, pero no la síntesis de proteínas, son necesarios para la señalización de mTORC2.
- El mTORC2 activo se asocia físicamente con los ribosomas.
- La señalización PI3K estimulada por insulina mejora la unión del mTORC2-ribosoma.
- La asociación mTORC2-ribosoma es vital en la señalización oncogénica de PI3K en las células cancerosas.
Conclusiones:
- Los ribosomas activan directamente el mTORC2.2.
- La interacción del mTORC2-ribosoma es un mecanismo conservado para la activación del mTORC2.
- Este mecanismo regulador asegura que la actividad de mTORC2 está vinculada a la capacidad de crecimiento celular.
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