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La disección a nivel de sistema del oscilador del ciclo celular: eludir la retroalimentación positiva produce
Joseph R Pomerening1, Sun Young Kim, James E Ferrell
1Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, California 94305, USA. pomereni@stanford.edu
Cell
|August 27, 2005
Resumen
Los ciclos de retroalimentación positiva son cruciales para las oscilaciones del ciclo celular embrionario, asegurando el tiempo adecuado para la destrucción de ciclinas y la progresión del ciclo celular. La interrupción de estos bucles conduce a oscilaciones más rápidas y amortiguadas, lo que afecta la división celular y la replicación del ADN.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología de Sistemas Biología de Sistemas.
- Biología del desarrollo Biología del desarrollo.
Sus antecedentes:
- La progresión del ciclo celular se basa en bucles de retroalimentación, incluido un bucle de retroalimentación negativa que involucra a Cdc2 y el complejo promotor de anafase (APC).
- Si bien la retroalimentación negativa puede generar oscilaciones, el papel de la retroalimentación positiva en el sistema Cdc2 / APC no estaba claro.
Objetivo del estudio:
- Para evaluar la importancia funcional de los bucles de retroalimentación positiva en el oscilador del ciclo celular embrionario.
- Comprender cómo las combinaciones de subcircuitos de retroalimentación generan un comportamiento oscilatorio.
Principales métodos:
- Manipulación experimental para "cortocircuitar" la retroalimentación positiva en el sistema Cdc2/APC.
- Análisis de los cambios resultantes en las oscilaciones de la actividad Cdc2 y sus efectos aguas abajo.
Principales resultados:
- El cortocircuito de retroalimentación positiva resultó en oscilaciones más rápidas, menos abruptas y amortiguadas en la actividad de Cdc2.
- Esta interrupción comprometió la destrucción de ciclinas, la salida mitótica y la replicación del ADN.
Conclusiones:
- Los circuitos de retroalimentación positiva juegan un papel crítico a nivel de sistemas en el ciclo celular embrionario.
- Las oscilaciones surgen de la interacción de retroalimentación positiva y negativa, similar a las neuronas marcapasos.
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