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Un modelo cuantitativo para la desfosforilación ordenada del sustrato Cdk durante la salida mitótica
Céline Bouchoux1, Frank Uhlmann
1Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, London WC2A 3LY, UK.
Cell
|November 15, 2011
Resumen
La salida mitótica implica eventos ordenados. En la levadura en ciernes, los distintos tiempos de desfosforilación del sustrato Cdk revelan cómo las actividades de la fosfatasa y la quinasa controlan la progresión del ciclo celular.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- La bioquímica es la bioquímica.
Sus antecedentes:
- La salida mitótica sigue a la separación de las cromatidas hermanas e implica la desfosforilación de numerosos sustratos por la cinasa dependiente de ciclina (Cdk).
- Los mecanismos precisos que rigen el orden temporal de estos eventos de desfosforilación durante la salida mitótica siguen siendo poco conocidos.
Objetivo del estudio:
- Para investigar el tiempo ordenado de la desfosforilación del sustrato de Cdk durante la salida mitótica en la levadura en ciernes.
- Para dilucidar los mecanismos que establecen la secuencia temporal de los eventos durante la salida mitótica.
Principales métodos:
- Experimentos in vivo que modulan las actividades de la cinasa dependiente de ciclina (Cdk) y la Cdc14 fosfatasa.
- Análisis cinético in vitro de la fosforilación y desfosforilación del sustrato de Cdk.
- Prueba de diferentes modelos para el ordenamiento temporal de los eventos de salida mitótica.
Principales resultados:
- La desfosforilación de los sustratos de Cdk involucrados en eventos secuenciales de salida mitótica ocurre con un tiempo ordenado.
- La proporción de fosfatasa a quinasa cambia gradualmente durante la salida mitótica.
- Los sustratos de Cdk responden a umbrales distintos de este cambio de relación, lo que lleva a una desfosforilación ordenada.
Conclusiones:
- El cambio gradual en la proporción de fosfatasa a quinasa proporciona un mecanismo cuantitativo para ordenar los eventos de salida mitótica.
- Este estudio ofrece una explicación mecanicista para un modelo cuantitativo de la progresión del ciclo celular.
- Los hallazgos en la levadura en ciernes proporcionan información sobre la regulación fundamental del ciclo celular.
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