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CBP: un coactivador transcripcional regulado por señal controlado por el calcio nuclear y la CaM quinasa IV
S Chawla1, G E Hardingham, D R Quinn
1Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
Science (New York, N.Y.)
|September 4, 1998
Resumen
Los factores de transcripción regulados por señales como CREB reclutan coactivadores como la proteína de unión CREB (CBP) para la expresión génica. Este estudio muestra que el reclutamiento de CBP se puede separar de la activación de la transcripción, revelando nuevas funciones reguladoras para el calcio nuclear y el cAMP.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Regulación genética Reglamento genético.
- La señalización celular de las células.
Sus antecedentes:
- El reclutamiento de coactivadores por factores de transcripción es esencial para la expresión génica.
- La proteína de unión a CREB (CBP) es un coactivador clave involucrado en la transcripción regulada por señales.
- Comprender los mecanismos precisos de reclutamiento y activación de CBP es crucial.
Objetivo del estudio:
- Para investigar el desacoplamiento del reclutamiento de la proteína de unión CREB (CBP) de la activación de la transcripción.
- Identificar las funciones reguladoras del calcio nuclear y la cAMP en la expresión génica dependiente de la CBP.
- Para caracterizar el dominio de activación transcripcional regulado por la señal de CBP.
Principales métodos:
- Utilizó la línea celular pituitaria del ratón AtT20.
- Examinó la fosforilación de CREB en la serina-133 como un paso de reclutamiento.
- Investigó los efectos de las señales citoplasmáticas de calcio y la señalización Ras en la actividad de la CBP.
- Se evaluó la transcripción mediada por CREB y CBP.
Principales resultados:
- Se demostró que el reclutamiento de la proteína de unión CREB (CBP) puede desacoplarse de la transcripción activada por CREB/CBP.
- Se identificó un dominio de activación transcripcional regulado por señal dentro de CBP.
- Se demostró que las señales de calcio citoplasmático que promueven el reclutamiento de CBP no aumentan la actividad o la transcripción de CBP.
- Destacó la influencia reguladora del calcio nuclear y el cAMP en la función del CBP.
Conclusiones:
- La proteína de unión a CREB (CBP) funciona como un coactivador transcripcional regulado por la señal.
- El calcio nuclear y la cAMP desempeñan funciones reguladoras distintas en la expresión génica dependiente de la CBP.
- Los hallazgos proporcionan una comprensión más profunda de los mecanismos moleculares que controlan la transcripción génica.
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