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La regulación a la baja de la PP2A ((Cdc55) fosfatasa por separación inicia la salida mitótica en las levaduras en
Ethel Queralt1, Chris Lehane, Bela Novak
1Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.
Cell
|May 23, 2006
Resumen
La activación de la separasa en la anafase baja la regulación de una fosfatasa, permitiendo que la cinasa dependiente de ciclina (Cdk) fosforilice Net1 y libere la fosfatasa Cdc14, promoviendo la salida mitótica en la levadura en ciernes.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- La bioquímica es la bioquímica.
Sus antecedentes:
- La actividad de la cinasa mitotica dependiente de la ciclina (Cdk) debe disminuir para salir de la mitosis.
- En la levadura en ciernes, la activación de la Cdc14 fosfatasa es crucial para la salida mitótica.
- Cdc14 es inhibido por Net1 en el nucleolo hasta la anafase.
Objetivo del estudio:
- Para dilucidar el mecanismo de la fosforilación Net1 durante la anafase.
- Comprender cómo se activa Cdc14 a medida que disminuye la actividad de Cdk.
- Presentar un modelo cuantitativo para la salida mitótica en la levadura en ciernes.
Principales métodos:
- Interacciones proteína-proteína investigadas entre la separasa, PP2A(Cdc55), y Net1.
- Utilizó la levadura en ciernes (S. cerevisiae) como organismo modelo.
- Desarrolló un modelo cuantitativo para la salida mitótica.
Principales resultados:
- La PP2A ((Cdc55) fosfatasa mantiene a Net1 en un estado subfosforilado durante la metafase.
- La separaza activada por anafase desregula hacia abajo PP2A (((Cdc55).
- La regulación a la baja de PP2A ((Cdc55) mediada por separación facilita la fosforilación Net1 y la fosforilación Bfa1 dependientes de Cdk, activando la red de salida mitótica.
Conclusiones:
- La inhibición dependiente de la separación de PP2A ((Cdc55) es un paso clave para iniciar la fosforilación Net1 y la posterior liberación de Cdc14.
- Este mecanismo asegura la salida mitótica oportuna incluso cuando la actividad de Cdk disminuye.
- Los hallazgos proporcionan un nuevo marco para comprender la regulación del ciclo celular y la progresión mitótica.
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