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Analysis of Cell Cycle Position in Mammalian Cells
Published on: January 21, 2012
El APC/C y el CBP/p300 cooperan para regular la transcripción y la progresión del ciclo celular
Andrew S Turnell1, Grant S Stewart, Roger J A Grand
1Cancer Research UK Institute for Cancer Studies, The Medical School, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. A.S.Turnell@bham.ac.uk
Nature
|December 2, 2005
Resumen
El complejo promotor de anafase/ciclosoma (APC/C) interactúa con los coactivadores de CBP/p300, influyendo en la progresión y transcripción del ciclo celular. Esta interacción es crucial para la función APC/C e impacta en la transformación celular.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- La bioquímica es la bioquímica.
Sus antecedentes:
- El complejo promotor de anafase / ciclosoma (APC / C) es una ligasa ubiquitina E3 clave que regula la progresión del ciclo celular a través de la mitosis y G1.
- Si bien su papel en el control del ciclo celular está establecido, otras funciones APC / C siguen siendo menos comprendidas.
Objetivo del estudio:
- Investigar nuevas funciones de los componentes APC/C más allá de la regulación del ciclo celular.
- Aclarar la interacción entre APC/C y los coactivadores CBP/p300 y sus consecuencias funcionales.
Principales métodos:
- Pruebas de interacción proteína-proteína para estudiar la unión APC5/APC7 y CBP/p300.
- Pruebas para medir la actividad de la acetiltransferasa CBP/p300 y la actividad transcripcional.
- Interferencia mediada por ARN para evaluar el papel de la CBP en la función APC/C.
- Análisis de la transformación celular mediada por E1A.
Principales resultados:
- Los componentes APC/C APC5 y APC7 interactúan directamente con los coactivadores CBP y p300 a través de dominios conservados.
- Esta interacción mejora la actividad de la acetiltransferasa CBP/p300 y potencia la transcripción.
- APC5 y APC7 suprimen la transformación mediada por E1A de una manera dependiente de CBP/p300.
- La CBP es esencial para la actividad APC/C, ya que su agotamiento reduce la actividad de la E3 ligasa y la progresión mitótica.
Conclusiones:
- Los componentes APC/C APC5 y APC7 forman complejos funcionales con CBP/p300, impactando la transcripción y la transformación celular.
- Estos hallazgos revelan nuevas funciones para APC/C en la regulación del crecimiento y sugieren que los componentes de APC/C pueden ser un objetivo durante la transformación.
- La CBP es un regulador crítico de la actividad de la APC/C ubiquitina ligasa y la progresión del ciclo celular.
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