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APC ((Cdc20) promueve la salida de la mitosis mediante la destrucción del inhibidor de la anafase Pds1 y la ciclina
M Shirayama1, A Tóth, M Gálová
1Research Institute of Molecular Pathology, Vienna, Austria.
Nature
|January 26, 2000
Resumen
El complejo promotor de anafase / ciclosoma (APC / C) controla la división celular. En la levadura, APC/C se dirige a la degradación de Pds1 para la liberación de Cdc14, crucial para la salida mitótica y la proliferación celular.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- La bioquímica es la bioquímica.
Sus antecedentes:
- La proteólisis mediada por ubiquitina por el complejo promotor de anafase/ciclosoma (APC/C) es crítica para la progresión del ciclo celular.
- La actividad APC/C, regulada por subunidades como Cdc20 y Cdh1/Hct1, impulsa la separación de las cromatidas hermanas y la salida mitótica.
- La Cdc14 fosfatasa es esencial para la salida mitótica, que implica la activación de Cdh1 y la acumulación de Sic1, pero su mecanismo de liberación sigue sin estar claro.
Objetivo del estudio:
- Para aclarar el papel de APC/C unido por Cdc20 (APC(Cdc20)) en la activación de la Cdc14 fosfatasa.
- Investigar cómo la proteólisis mediada por APC (((Cdc20) contribuye a la salida mitótica y la proliferación celular en Saccharomyces cerevisiae.
- Determinar los sustratos específicos de APC ((Cdc20) que son esenciales para la activación de Cdc14 y los sucesos posteriores del ciclo celular.
Principales métodos:
- Genética de levadura utilizada en Saccharomyces cerevisiae.
- Se han investigado las vías de degradación de proteínas mediadas por el complejo promotor de anafase/ciclosoma (APC/C).
- Se analizaron las funciones de Pds1, Clb5, Cdc14, Cdc20, Cdh1 y Sic1 en la mitosis.
Principales resultados:
- APC(Cdc20) media en la degradación de Pds1 y la ciclina de fase S Clb5.5.
- La degradación de Pds1 es necesaria para la liberación de Cdc14 fosfatasa desde el núcleo.
- La degradación de Clb5 es esencial para que Cdc14 inactive Cdk1 y active Cdh1 y Sic1, promoviendo la salida mitótica.
- Las células que carecen tanto de Pds1 como de Clb5 pueden proliferar sin Cdc20.
Conclusiones:
- APC ((Cdc20) juega un doble papel en la promoción de la salida mitótica mediante la degradación de Pds1 y Clb5.
- La degradación de Pds1 por APC ((Cdc20) es un requisito previo para la liberación de Cdc14, mientras que la degradación de Clb5 es crucial para las funciones aguas abajo de Cdc14.
- Los hallazgos revelan un mecanismo regulador crítico para la salida mitótica y resaltan la redundancia de la función APC / C en antecedentes mutantes específicos.
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