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Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding
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Mutantes de los receptores de glucocorticoides que son activadores constitutivos de la mejora de la transcripción
Nature
|January 22, 1987
Resumen
Los receptores de glucocorticoides se unen al ADN y activan la expresión génica. Los nuevos mutantes de los receptores muestran que esta función es constitutiva, lo que sugiere que la unión a las hormonas desenmascara los dominios preexistentes de unión al ADN y potenciadores.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Endocrinología Endocrinología.
- Genética La genética.
Sus antecedentes:
- Los glucocorticoides son hormonas esteroides que se unen a los receptores intracelulares.
- La unión al receptor induce un cambio conformacional, lo que permite la unión al ADN y la mejora de la transcripción a través de los elementos de respuesta a los glucocorticoides (GREs).
- El papel preciso de esta "transformación del receptor" en la actividad biológica sigue sin estar claro.
Objetivo del estudio:
- Para investigar el significado funcional de la transformación del receptor de glucocorticoides.
- Caracterizar los nuevos mutantes de los receptores que exhiben la función constitutiva de potenciador del GRE.
Principales métodos:
- Utilizó secuencias de codificación de los receptores de glucocorticoides de ratas clonadas para generar mutantes.
- Se emplean ensayos de transfección génica en las células para evaluar la actividad del potenciador GRE.
- Realizó estudios de mapeo para diferenciar los dominios de unión del ADN y las hormonas.
Principales resultados:
- Se han desarrollado mutantes de los receptores que constitutivamente provocan la función del potenciador GRE sin hormonas.
- Se demostró que estos mutantes activan la transcripción independientemente de la unión del ligando.
- Los estudios de mapeo distinguen los dominios de unión al ADN y los de unión a las hormonas.
Conclusiones:
- La transformación de los receptores tras la unión a las hormonas puede desenmascarar principalmente dominios funcionales preexistentes.
- Estos dominios son responsables de la unión al ADN y / o la activación del potenciador.
- La actividad constitutiva en los mutantes apoya la hipótesis de desenmascarar dominios funcionales.
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