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Se requiere una superficie de unión al factor de transcripción del coactivador p300 para la hematopoyesis
Lawryn H Kasper1, Fayçal Boussouar, Paul A Ney
1Department of Biochemistry, St Jude Children's Research Hospital, 332 North Lauderdale, Memphis, Tennessee 38105, USA.
Nature
|October 18, 2002
Resumen
Los dominios KIX de los coactivadores CBP y p300 tienen roles distintos en el desarrollo del ratón. La alteración del dominio KIX de p300 afecta la formación de células sanguíneas, mientras que las mutaciones del dominio KIX de CBP tienen efectos mínimos.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología del desarrollo Biología del desarrollo.
- Genética La genética.
Sus antecedentes:
- La CBP (proteína de unión al CREB) y la p300 son coactivadores críticos involucrados en la regulación de los genes.
- Estas proteínas poseen moléculas adaptadoras y funciones de proteína acetiltransferasa esenciales para el desarrollo normal.
- Las mutaciones en CBP y p300 están relacionadas con varios tipos de cáncer, incluidos los tumores hematopoyéticos y epiteliales.
Objetivo del estudio:
- Para investigar las funciones in vivo de los coactivadores CBP y p300.
- Determinar las funciones esenciales de los dominios KIX de CBP y p300 en el desarrollo de los mamíferos.
- Para aclarar las funciones específicas de los dominios CBP y p300 KIX en la regulación hematopoyética.
Principales métodos:
- Generación de ratones con mutaciones puntuales dirigidas en los dominios KIX de CBP y p300.
- Análisis del desarrollo hematopoyético y defectos multilineales en ratones mutantes.
- Estudios de interacción genética que involucran mutaciones en los dominios c-Myb y p300 KIX.
Principales resultados:
- Los ratones con dominios KIX p300 alterados presentan graves defectos hematopoyéticos multilineales, incluyendo anemia y deficiencia de células B.
- Las mutaciones en el dominio CBP KIX no causan anormalidades de desarrollo significativas en ratones.
- Una interacción genética sinérgica entre las mutaciones de dominio KIX de c-Myb y p300 pone de relieve el papel crítico de la unión de c-Myb a p300 en el desarrollo de los megacariocitos.
Conclusiones:
- Los dominios KIX de CBP y p300 poseen funciones no redundantes y contrastantes in vivo, particularmente en la hematopoyesis.
- La unión del factor de transcripción c-Myb al dominio p300 KIX es crucial para el desarrollo y la función de los megacariocitos.
- Estos hallazgos revelan roles especializados para coactivadores altamente relacionados en la regulación de procesos biológicos complejos.
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