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Glicosilación dinámica del factor de transcripción CREB: un papel potencial en la regulación génica
Nathan Lamarre-Vincent1, Linda C Hsieh-Wilson
1Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Journal of the American Chemical Society
|May 29, 2003
Resumen
La proteína de unión al elemento sensible a la AMP cíclica (CREB), vital para la memoria, se somete a la glicosilación de O-GlcNAc en el cerebro. Esta modificación obstaculiza el CREB.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología Molecular Biología Molecular
- La bioquímica es la bioquímica.
Sus antecedentes:
- CREB (proteína de unión al elemento sensible a la AMP cíclica) es un factor de transcripción crucial para la formación de la memoria a largo plazo.
- La glicosilación de O-GlcNAc es una modificación dinámica post-traduccional involucrada en varios procesos celulares.
Objetivo del estudio:
- Para investigar si CREB es O-GlcNAc glicosilado en el cerebro de los mamíferos.
- Determinar las consecuencias funcionales de la glicosilación de CREB O-GlcNAc en su actividad transcripcional.
Principales métodos:
- Western blotting para detectar la modificación de O-GlcNAc en el CREB.
- Ensayos in vitro para evaluar la interacción de CREB con TAFII130 y su actividad transcripcional.
Principales resultados:
- Se ha demostrado que CREB es O-GlcNAc glicosilado en dos sitios específicos dentro de su dominio Q2.
- Este evento de glicosilación interrumpe la interacción entre CREB y la proteína TAFII130.
- La glicosilación O-GlcNAc de CREB conduce a la represión de su actividad transcripcional in vitro.
Conclusiones:
- La glicosilación de O-GlcNAc juega un papel regulador en la expresión génica dentro del cerebro.
- Los hallazgos establecen un vínculo entre la modificación de O-GlcNAc y los mecanismos moleculares subyacentes a la memoria y el almacenamiento de información.
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