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La inhibición de la transcripción por un receptor glucocorticoide de la proteína de fusión
A E Oro1, S M Hollenberg, R M Evans
1Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, California 92138.
Cell
|December 23, 1988
Resumen
Los receptores de la hormona esteroide usan la regulación transcripcional negativa para equilibrar los procesos celulares. Los investigadores identificaron regiones clave del receptor humano de glucocorticoides esenciales para la represión de la actividad génica específica, lo que sugiere un método general para crear represores transcripcionales.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Genética La genética.
- Endocrinología Endocrinología.
Sus antecedentes:
- Las hormonas esteroides regulan las funciones celulares cruciales, incluyendo el desarrollo y la homeostasis.
- La regulación transcripcional negativa es vital para equilibrar los efectos estimulantes de los esteroides.
- El receptor glucocorticoide humano (hGR) juega un papel clave en la mediación de las respuestas a los esteroides.
Objetivo del estudio:
- Para identificar regiones del receptor glucocorticoide humano esenciales para la transrepresión.
- Para investigar el mecanismo de la regulación transcripcional negativa por hGR.
- Explorar el potencial para crear nuevos represores transcripcionales específicos de la secuencia.
Principales métodos:
- Se utilizaron mutantes de los receptores de glucocorticoides humanos.
- Represión evaluada del gen que codifica la subunidad alfa de la gonadotropina coriónica.
- Proteínas de fusión construidas y probadas que incorporan partes de hGR y otros genes.
Principales resultados:
- Los dominios de unión al ADN y a los ligandos de hGR son críticos para la represión.
- El amino terminus no es esencial para esta función represiva.
- El extremo carboxilo puede ser reemplazado funcionalmente por polipéptidos del receptor de mineralocorticoides o beta-galactosidasa, apoyando un modelo de impedimento estérico.
Conclusiones:
- El receptor glucocorticoide humano reprime la transcripción a través de un mecanismo de impedimento estérico.
- Estos hallazgos proporcionan una base para el desarrollo de represores transcripcionales específicos de la secuencia.
- Comprender la función de la hGR ofrece información sobre la acción de las hormonas esteroides y la regulación génica.
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