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Las colisiones de ribosomas desencadenan respuestas generales al estrés para regular el destino celular
Colin Chih-Chien Wu1, Amy Peterson2, Boris Zinshteyn1
1Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Cell
|July 2, 2020
Resumen
Las colisiones de ribosomas desencadenan respuestas de estrés celular, activando las vías de la proteína quinasa activada por el estrés (SAPK) y GCN2. La proteína ZAK actúa como un sensor para estas colisiones, iniciando la señalización inmediata.
Área de la Ciencia:
- Biología molecular
- Señalización celular
- Las vías de respuesta al estrés
Sus antecedentes:
- Los problemas de traducción de ARNm causan el estancamiento y las colisiones de los ribosomas, iniciando el control de calidad celular.
- La respuesta celular más amplia a las colisiones de ribosomas sigue siendo en gran medida inexplorada.
Objetivo del estudio:
- Para investigar la respuesta celular global a las colisiones de los ribosomas.
- Identificar los mecanismos moleculares que vinculan las colisiones de los ribosomas con la transducción de señales.
Principales métodos:
- Utilizó inhibidores del alargamiento de la traducción y condiciones de estrés celular (hambre de aminoácidos, irradiación UV).
- Utilizó perfiles selectivos de ribosomas y ensayos bioquímicos.
- Investigó el papel de la proteína MAPKKK ZAK.
Principales resultados:
- Las colisiones de ribosomas activan la proteína quinasa activada por estrés (SAPK) y las respuestas al estrés mediadas por GCN2.
- La proteína MAPKKK ZAK sirve como un sensor para las colisiones de ribosomas.
- ZAK se autofosforila específicamente en los disomas (la unidad mínima de colisión del ribosoma) y es crucial para la activación de SAPK y GCN2.
Conclusiones:
- Las colisiones de ribosomas se identifican como desencadenantes clave de las vías de transducción de señales.
- ZAK es una proteína centinela crítica que detecta las colisiones de ribosomas e inicia la señalización de estrés.
- Estos hallazgos proporcionan información molecular sobre cómo las interrupciones en la homeostasis traslacional influyen en el destino celular.
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