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Una vía evolucionariamente conservada controla la homeostasis del proteasoma
Nature
|July 28, 2016
Resumen
Una vía de señalización conservada regula los niveles de proteasomas. La inhibición de TORC1 activa Mpk1, aumentando los componentes del proteasoma para la supervivencia celular bajo estrés. Esta vía se conserva en los mamíferos.
Área de la Ciencia:
- Biología celular
- Biología molecular
- La bioquímica
Sus antecedentes:
- El proteosoma es crucial para la degradación de las proteínas, sin embargo, los mecanismos que mantienen su abundancia (homeostasis del proteosoma) no se comprenden completamente.
- Los niveles de proteasomas celulares deben estar estrictamente regulados para satisfacer las demandas celulares de rotación de proteínas.
Objetivo del estudio:
- Para aclarar las vías de señalización que rigen la homeostasis del proteasoma.
- Identificar los reguladores clave que controlan la subunidad del proteasoma y la producción de chaperones de ensamblaje.
Principales métodos:
- Se emplearon técnicas de genética de levadura y biología molecular para estudiar el papel de TORC1 y Mpk1.
- Se utilizaron cultivos celulares de mamíferos y análisis moleculares para evaluar la conservación evolutiva.
Principales resultados:
- La inhibición de TORC1 (objetivo del complejo de rapamicina 1) en la levadura indujo la expresión de 19 chaperonas de ensamblaje de partículas reguladoras (RAC) y subunidades proteasómicas.
- A continuación de TORC1, se activó la vía Mpk1 (proteína quinasa activada por mitógeno), aumentando los RAC y las subunidades del proteasoma, manteniendo así la degradación proteasómica y la viabilidad celular bajo estrés.
- Se encontró que la vía que involucra a mTOR (TOR de mamíferos) y ERK5 (cinasa regulada por señales extracelulares 5) se conserva en los mamíferos, controlando los niveles de RAC y la abundancia de proteasomas.
Conclusiones:
- Una vía de señalización conservada, que involucra a TORC1 / mTOR y Mpk1 / ERK5, ajusta rápidamente la abundancia de proteasomas en respuesta a las necesidades y el estrés celular.
- Esta respuesta adaptativa es vital para mantener la degradación proteasómica y la viabilidad celular.
- Dirigirse a esta vía presenta una estrategia terapéutica potencial para enfermedades caracterizadas por una degradación proteasómica deteriorada.
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