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Un complejo transcripcionalmente [corrección de transcripción] activo de APP con Fe65 y la histona acetiltransferasa
1The Center for Basic Neuroscience, Department of Molecular Genetics, and Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9111 USA.
Science (New York, N.Y.)
|July 7, 2001
Resumen
La cola citoplasmática de la proteína precursora de amiloide-beta (APP) se une a Fe65 y Tip60, activando la transcripción génica. Esto sugiere APP.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología Molecular Biología Molecular
- Genética La genética.
Sus antecedentes:
- La proteína precursora de amiloide-beta (APP) es escindida por la gamma-secretasa, liberando un fragmento intracelular.
- Actualmente se desconoce la función fisiológica de este fragmento de cola citoplasmática APP liberado.
- La enfermedad de Alzheimer se caracteriza por la acumulación de beta-péptido amiloide, derivado de APP.
Objetivo del estudio:
- Para investigar la función de la cola citoplasmática de la proteína precursora de la amiloide-beta (APP).
- Para determinar si la cola citoplasmática de la APP interactúa con otras proteínas celulares.
- Explorar el papel de los productos de escisión de la APP en la regulación génica.
Principales métodos:
- Investigó la interacción de la cola citoplasmática de la APP con las proteínas nucleares.
- Utilizó ensayos de co-inmunoprecipitación para detectar complejos proteicos.
- Se evaluó la actividad transcripcional utilizando ensayos de genes reporteros con dominios de unión a Gal4- y LexA-DNA.
Principales resultados:
- Se demostró que la cola citoplasmática de APP forma un complejo multimérico con Fe65 y Tip60.
- Se demostró que este complejo APP-Fe65-Tip60 estimula significativamente la transcripción.
- Se indicó que la escisión de la gamma-secretasa de APP libera el fragmento de la cola, lo que podría regular la expresión génica.
Conclusiones:
- La cola citoplasmática de APP, cuando es liberada por la gamma-secretasa, puede formar un complejo funcional con Fe65 y Tip60.
- Este complejo actúa como un potente activador transcripcional, lo que sugiere un papel para los fragmentos intracelulares de APP en la expresión génica.
- Estos hallazgos proporcionan nuevos conocimientos sobre las funciones no amiloidogénicas de APP y sus productos de procesamiento.
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