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Interacción de la acetiltransferasa EP300 y el sistema proteasómico en la regulación del factor de transcripción 1
Swasti Raychaudhuri1, Christian Loew1, Roman Körner1
1Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
Cell
|March 4, 2014
Resumen
Las células de los mamíferos activan las respuestas al estrés para mantener la homeostasis de las proteínas, involucrando el factor de transcripción de choque térmico 1 (HSF1). Este estudio identifica EP300 y los proteasomas nucleares como reguladores clave de la actividad de HSF1 y la respuesta al estrés.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- Mecanismos de respuesta al estrés.
Sus antecedentes:
- Las células de los mamíferos activan las respuestas al estrés citosólico bajo condiciones proteotóxicas para mantener la homeostasis de las proteínas.
- La expresión de la chaperona dependiente del factor de transcripción de choque térmico 1 (HSF1) es crucial para esta respuesta.
Objetivo del estudio:
- Identificar los moduladores de la inducción y atenuación de la respuesta al estrés utilizando una pantalla de interferencia de ARN en las células HeLa.
- Aclarar las funciones reguladoras de las proteínas identificadas en las respuestas al estrés mediadas por HSF1.
Principales métodos:
- Pantalla de interferencia de ARN (RNAi) en las células HeLa.
- Análisis de la localización y función de las proteínas en los compartimentos celulares.
- Investigación de las vías de acetilación y degradación proteasomales de HSF1.
Principales resultados:
- Las proteínas moduladoras se encuentran en varios compartimentos celulares, destacando los modificadores de cromatina y el control de calidad de las proteínas nucleares.
- La acetiltransferasa EP300 estabiliza el HSF1 activable a través de la acetilación de lisina no funcional, evitando la degradación proteasómica.
- La acetilación de las lisinas críticas ajusta la activación de HSF1 durante el estrés.
- El sistema proteasómico nuclear atenúa la respuesta al estrés mediante la degradación de HSF1 activado, relacionado con el aclaramiento de proteínas mal plegadas.
Conclusiones:
- EP300 y los proteasomas nucleares son reguladores críticos de la respuesta al estrés celular mediante la modulación de la actividad HSF1.
- La regulación de la HSF1 implica un equilibrio entre la estabilización a través de la acetilación y la atenuación a través de la degradación proteasoma.
- Comprender estos mecanismos proporciona información sobre el mantenimiento de la homeostasis de las proteínas bajo estrés.
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