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Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
Bases estructurales para la regulación redox de la localización del factor de transcripción Yap1
Matthew J Wood1, Gisela Storz, Nico Tjandra
1Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-5430, USA.
Nature
|August 20, 2004
Resumen
El factor de transcripción Yap1 controla la expresión génica durante el estrés oxidativo. Su estructura cambia a través de enlaces disulfuro, regulando su movimiento entre el núcleo y el citoplasma.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
- La bioquímica es la bioquímica.
Sus antecedentes:
- Los organismos deben adaptar la expresión génica a los cambios ambientales para sobrevivir.
- El factor de transcripción Yap1 es clave para manejar las respuestas al estrés oxidativo en Saccharomyces cerevisiae.
- La Yap1 activada se mueve hacia el núcleo, influyendo en hasta 70 genes.
Objetivo del estudio:
- Para identificar un dominio regulado por redox dentro de Yap1.1.
- Para determinar la estructura de la solución de alta resolución de este dominio.
- Para dilucidar el mecanismo de control de localización subcelular de Yap1.
Principales métodos:
- Técnicas de biología estructural para determinar la estructura de la solución de Yap1.
- Pruebas bioquímicas para investigar las interacciones redox-dependientes.
- Mutagénesis dirigida al sitio para sondear dominios funcionales.
Principales resultados:
- Se identificó y caracterizó estructuralmente un dominio regulado por redox en Yap1.
- En su estado oxidado, la señal de exportación nuclear (NES) de Yap1 está enmascarada por enlaces de disulfuro.
- La interrupción de las interacciones hidrofóbicas impidió los cambios de localización regulados por redox.
- La reducción de los enlaces disulfuro conduce a una conformación no estructurada, exponiendo el NES y permitiendo la redistribución citoplasmática.
Conclusiones:
- El estudio revela la base estructural para la localización de Yap1 dependiente de redox.
- Se presenta un nuevo mecanismo de regulación del factor de transcripción a través de enlaces disulfuro reversibles.
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