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El activador dependiente de la proteína-cinasa-A en el factor de transcripción CREB revela un nuevo papel para los
P Brindle1, S Linke, M Montminy
1Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California 92037.
Nature
|August 26, 1993
Resumen
Las señales hormonales activan el factor de transcripción CREB mediante la fosforilación de su dominio inducible por kinasa (KID). Esta fosforilación mejora la transcripción génica, incluso cuando el KID está en una molécula separada.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- La señalización celular.
Sus antecedentes:
- El AMP cíclico (cAMP) es un segundo mensajero clave en las vías de señalización celular.
- El factor de transcripción CREB (proteína de unión del elemento de respuesta CAMP) regula la expresión génica en respuesta a la cAMP.
- La fosforilación de CREB en la serina 133 por la proteína quinasa A es crucial para su actividad transcripcional.
Objetivo del estudio:
- Investigar el papel del dominio inducible por kinasa (KID) del CREB en la mediación de la activación transcripcional inducida por CAMP.
- Para determinar si el KID puede conferir la inducibilidad de la cAMP a otros dominios de activación de la transcripción.
- Explorar el potencial de KID como una nueva clase de activadores transcripcionales condicionales.
Principales métodos:
- Se crearon construcciones de proteínas de fusión para probar la función del CREB KID.
- El KID estaba unido a dominios de activación heterólogos (CREB Q2, GAL4, GCN4).
- Se utilizaron ensayos de genes reporteros para medir la actividad transcripcional en respuesta a la estimulación de la cAMP.
Principales resultados:
- El CREB KID por sí solo fue suficiente para conferir la activación transcripcional inducible por CAMP.
- Este efecto se observó cuando el KID se fusionó con diferentes dominios de activación.
- La función del KID era independiente de su localización intracelular o de su actividad de unión al ADN.
- Sorprendentemente, el KID mantuvo su función incluso cuando estaba atado a un polipéptido separado en un sitio promotor adyacente.
Conclusiones:
- El KID es un dominio funcional crítico que media la respuesta del CREB al cAMP.
- El KID representa un nuevo mecanismo para la activación transcripcional condicional.
- Este dominio puede funcionar interactuando con otros factores vinculados al promotor para mejorar la expresión génica.
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