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La proliferación, pero no el crecimiento, está bloqueada por la deleción condicional de la proteína ribosómica 40S S6
S Volarevic1, M J Stewart, B Ledermann
1Friedrich Miescher Institute, Maulbeerstrasse 66, CH-4058, Basel, Switzerland.
Science (New York, N.Y.)
|June 17, 2000
Resumen
La biogénesis del ribosoma es vital para el crecimiento celular. La interrupción de la producción de ribosomas 40S en el hígado de ratones inesperadamente permitió el crecimiento pero bloqueó la proliferación celular, lo que sugiere un punto de control del ciclo celular.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- La bioquímica es la bioquímica.
Sus antecedentes:
- La biogénesis del ribosoma es crucial para la proliferación celular.
- Pueden existir mecanismos celulares para detectar y responder a las interrupciones en la producción de ribosomas.
- La proteína ribosómica 40S S6 es esencial para la biogénesis de los ribosomas 40S.
Objetivo del estudio:
- Investigar el papel de la biogénesis del ribosoma 40S en la proliferación de las células hepáticas y el control del ciclo celular.
- Para determinar si los defectos en la biogénesis del ribosoma desencadenan una respuesta de punto de control.
Principales métodos:
- Eliminación condicional del gen que codifica 40S proteína ribosómica S6 en el hígado de ratón adulto.
- Protocolos de ayuno y realimentación de nutrientes.
- Hepatitectomía parcial para inducir la regeneración del hígado.
- Análisis de marcadores de proliferación celular (por ejemplo, ciclina E) y complejos del ciclo celular (por ejemplo, ciclina D-CDK4).
Principales resultados:
- Los hígados deficientes en la proteína ribosómica 40S S6 exhibieron un crecimiento impulsado por nutrientes a pesar de la biogénesis de ribosomas abolida.
- Las células hepáticas no pudieron proliferar o inducir la expresión de ciclina E después de la hepatectomía parcial.
- Se formaron complejos activos de ciclina D-CDK4, pero se inhibió la progresión del ciclo celular.
Conclusiones:
- La abrogación de la biogénesis del ribosoma 40S puede inducir un control de punto de control que impide la progresión del ciclo celular.
- Esto sugiere un mecanismo de vigilancia que vincula la producción de ribosomas con la regulación del ciclo celular.
- La interrupción de la biogénesis del ribosoma impone un bloqueo a la proliferación de las células hepáticas, independientemente de la disponibilidad de nutrientes.
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