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La activación sinérgica por los dominios ricos en glutamina del factor de transcripción Sp1 humano
A J Courey1, D A Holtzman, S P Jackson
1Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Cell
|December 1, 1989
Resumen
Las interacciones proteína-proteína que involucran a Sp1 (proteína de especificidad 1) mejoran la transcripción. Los monómeros Sp1 interactúan, lo que permite la activación sinérgica incluso desde sitios de ADN distantes o con mutantes con deficiencia de unión al ADN.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Genética La genética.
- La bioquímica es la bioquímica.
Sus antecedentes:
- La proteína de especificidad 1 (Sp1) es un factor de transcripción humano.
- Sp1 utiliza dominios de activación ricos en glutamina, un motivo que también se encuentra en otros activadores como Drosophila Antennapedia.
- Sp1 es típicamente considerado un factor promotor proximal.
Objetivo del estudio:
- Investigar el papel de las interacciones proteína-proteína en la modulación de la actividad de Sp1.
- Para explorar si Sp1 puede activar la transcripción desde sitios distales del ADN.
- Para determinar si los mutantes Sp1 pueden influir en la actividad transcripcional.
Principales métodos:
- Fusión de segmentos de proteínas de Drosophila Antennapedia con el dominio de unión del ADN Sp1.
- Análisis de la unión de Sp1 a los sitios promotores proximales y distales.
- Utilizando un mutante Sp1 con deficiencia de unión al ADN.
- Enlace cruzado de glutaraldehído para detectar las interacciones de proteínas.
Principales resultados:
- Los dominios ricos en glutamina de diferentes proteínas pueden funcionar como potentes activadores.
- Sp1 unido a sitios distales y proximales puede estimular sinérgicamente la transcripción.
- Un mutante Sp1 con deficiencia de unión al ADN puede interactuar con Sp1 unido para superactivar la transcripción.
- La evidencia directa de las interacciones del monómero Sp1 se obtuvo a través de la vinculación cruzada de glutaraldehído.
Conclusiones:
- Las interacciones Sp1-Sp1 son cruciales para modular la actividad del promotor.
- Las interacciones proteína-proteína influyen significativamente en la función transcripcional de Sp1.
- El motivo del dominio de activación rico en glutamina se conserva funcionalmente en todas las especies.
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