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El factor de transcripción Ojos ausentes es una proteína tirosina fosfatasa
Tina L Tootle1, Serena J Silver, Erin L Davies
1Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
Nature
|November 25, 2003
Resumen
La proteína de los ojos ausentes (Eya) actúa como una tirosina fosfatasa, regulando la transcripción génica. Esta actividad intrínseca de la fosfatasa es crucial para el desarrollo del ojo en Drosophila, revelando un nuevo mecanismo para el control de la transcripción.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
- Biología del desarrollo Biología del desarrollo.
Sus antecedentes:
- Las modificaciones postraslacionales regulan dinámicamente la función de las proteínas.
- La fosforilación de los factores de transcripción afecta su estabilidad, localización y actividad.
- La proteína de los ojos ausentes (Eya) es un factor de transcripción evolucionariamente conservado.
Objetivo del estudio:
- Para investigar la actividad enzimática de la proteína de los ojos ausentes (Eya).
- Determinar el papel de la actividad potencial de la fosfatasa de Eya en la función y el desarrollo de las proteínas.
- Para aclarar el mecanismo por el cual Eya modula la regulación transcripcional.
Principales métodos:
- Ensayos bioquímicos para probar la actividad de la proteína tirosina fosfatasa.
- Experimentos in vitro y basados en células utilizando células de Drosophila cultivadas.
- Mutagénesis dirigida al sitio para interrumpir el sitio activo de la fosfatasa putativa.
- Análisis del papel de Eya en el desarrollo del ojo de Drosophila utilizando cepas mutantes.
Principales resultados:
- Los ojos ausentes (Eya) muestran actividad intrínseca de la proteína tirosina fosfatasa.
- Eya puede autocatalíticamente desfosforilarse a sí mismo.
- Las mutaciones que inactivan el sitio activo de la fosfatasa perjudican la función de Eya en la especificación y el desarrollo del ojo.
- Eya pertenece a la superfamilia de la haloácida deshalogenasa (HAD) de las fosfatasas.
Conclusiones:
- Los ojos ausentes (Eya) funcionan como una proteína tirosina fosfatasa no basada en tiol.
- La actividad de la fosfatasa intrínseca de Eya es esencial para su papel como coactivador transcripcional en el desarrollo del ojo.
- Este descubrimiento revela un nuevo mecanismo para ajustar la regulación transcripcional a través de un factor de transcripción que contiene fosfatasa.
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