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Se requieren dos regiones funcionalmente diferentes en Fos para la interacción de ADN específica de la secuencia del
M Neuberg1, M Schuermann, J B Hunter
1Institut für Molekularbiologie und Tumorforschung, Phillips-Universität Marburg, FRG.
Nature
|April 13, 1989
Resumen
El complejo Fos/Jun se une al ADN para regular la transcripción génica. Regiones específicas en Fos, incluida la cremallera de leucina y una región básica adyacente, son cruciales para esta regulación de unión y transcripción del ADN.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Regulación genética Reglamento genético.
- Interacciones entre proteínas y ADN.
Sus antecedentes:
- El complejo Fos/Jun, formado por proteínas Fos celulares y retrovirales con el factor de transcripción AP1/Jun, se une a las secuencias de ADN TRE.
- Este evento de unión es crítico para estimular la transcripción génica.
Objetivo del estudio:
- Identificar las regiones específicas dentro de la proteína Fos esenciales para la formación del complejo funcional Fos/Jun/TRE.
- Para aclarar los roles de estas regiones en las interacciones proteína-proteína y proteína-ADN.
Principales métodos:
- Mutagénesis dirigida al sitio para introducir sustituciones específicas de aminoácidos en la proteína Fos.
- Análisis de la asociación entre las proteínas Fos y Jun.
- Evaluación de la formación del complejo Fos/Jun/TRE y la actividad de unión al ADN.
Principales resultados:
- Se requieren dos regiones distintas en Fos para la formación del complejo Fos/Jun/TRE: la cremallera de leucina para la asociación Jun y una región básica adyacente.
- Las sustituciones de aminoácidos en la región básica interrumpieron la unión de Fos/Jun al ADN TRE sin afectar la asociación de proteínas Fos/Jun.
- Los aminoácidos funcionalmente críticos en Fos comparten similitudes estructurales con los sitios de unión al ADN en Jun y GCN4.
Conclusiones:
- La región básica de Fos, adyacente a la cremallera de leucina, juega un papel crítico en la mediación de la unión al ADN del complejo Fos/Jun.
- La similitud estructural de esta región con otros dominios de unión al ADN pone de relieve los mecanismos conservados en la regulación transcripcional.
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