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El inhibidor de la ciclina quinasa tipo B p40SIC1 controla la transición de G1 a S en S. cerevisiae
E Schwob1, T Böhm, M D Mendenhall
1I. M. P. Research Institute of Molecular Pathology, Vienna, Austria.
Cell
|October 21, 1994
Resumen
La progresión del ciclo celular de la levadura requiere la activación de la cinasa Cdc28 tanto por ciclinas de tipo G1 como por ciclinas de tipo B. Este estudio revela que la proteólisis del inhibidor p40SIC1 es crucial para la transición de fase G1 a S.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- La bioquímica es la bioquímica.
Sus antecedentes:
- Las células de levadura inician procesos críticos como la formación de brotes, la duplicación del cuerpo del poste del huso y la replicación del ADN al alcanzar un tamaño específico.
- Estos eventos están regulados principalmente por la activación de la proteína quinasa Cdc28 a través de las ciclinas G1 (Cln1, -2, y -3).
Objetivo del estudio:
- Investigar el papel de las ciclinas de tipo B (Clb) en la replicación del ADN durante el ciclo celular de la levadura.
- Para aclarar el mecanismo que controla la transición de fase G1 a S, centrándose en la regulación de la actividad de Cdc28.
Principales métodos:
- Análisis de una cepa de levadura mutante clb1-6 sextuple.
- Comparación de los fenotipos mutantes con los mutantes cdc34 que carecen de una enzima conjugadora de ubiquitina.
- Investigación de los niveles de proteína p40SIC1 y la degradación en células de tipo silvestre y células mutantes.
Principales resultados:
- La replicación del ADN en la levadura depende de la activación de Cdc28 por parte de las ciclinas de tipo G1 y B.
- Un mutante sextuplo clb1-6 se detiene en la fase G1 con múltiples brotes, similar a los mutantes cdc34.
- El inhibidor p40SIC1 impide la entrada en la fase S al inhibir Cdc28 ligado a Clb y se degrada en la transición G1/S.
Conclusiones:
- La proteólisis oportuna del inhibidor de la cinasa dependiente de la ciclina p40SIC1 es esencial para la transición de la fase G1 a la fase S en la levadura.
- Las ciclinas de tipo B juegan un papel crítico en la activación de Cdc28 para la replicación del ADN.
- La regulación de la degradación del inhibidor es un mecanismo clave que controla la progresión del ciclo celular.
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