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Desempaquetar la respuesta proteica desplegada
Carolyn A Worby1, Jack E Dixon1
1Departments of Pharmacology, Cellular and Molecular Medicine, and Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
Cell
|September 13, 2014
Resumen
Los científicos Peter Walter y Kazutoshi Mori ganaron el premio Lasker por descubrir la base molecular de la respuesta proteica desplegada. Este sistema celular crucial mantiene la salud de las proteínas dentro del retículo endoplasmático.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
- La bioquímica es la bioquímica.
Sus antecedentes:
- El retículo endoplasmático (ER) es vital para la síntesis y el plegamiento de las proteínas.
- Las proteínas mal plegadas se acumulan en el ER durante el estrés celular, lo que representa una amenaza para la función celular.
- Se requiere un mecanismo celular adaptativo para manejar la proteostasis ER.
Objetivo del estudio:
- Para dilucidar los mecanismos moleculares que subyacen a la respuesta de la proteína desplegada (UPR).
- Comprender cómo las células detectan y señalan la presencia de proteínas mal plegadas en el retículo endoplasmático.
- Identificar las vías de señalización que conectan el estrés del retículo endoplasmático con las medidas correctivas nucleares.
Principales métodos:
- Utilizamos genética de levaduras y ensayos bioquímicos para diseccionar las vías de señalización de la UPR.
- Empleó técnicas de biología molecular para identificar sensores y transductores UPR clave.
- Investigó la regulación transcripcional y traslacional mediada por el UPR.
Principales resultados:
- Descubrió los actores moleculares clave y las cascadas de señalización de la UPR.
- Se demostró cómo la UPR detecta las proteínas desplegadas e inicia una respuesta celular.
- Reveló la intrincada comunicación entre el retículo endoplasmático y el núcleo para restaurar la proteostasis.
Conclusiones:
- El UPR es un sistema crítico de control de calidad intracelular esencial para la supervivencia celular bajo estrés.
- Comprender el UPR proporciona información sobre la patogénesis de las enfermedades relacionadas con el mal plegamiento de las proteínas.
- Estos descubrimientos allanan el camino para estrategias terapéuticas dirigidas a la UPR en diversas enfermedades humanas.
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