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La dinámica de la red de ligasa de ubiquitina de cullin-RING fue revelada por la proteómica cuantitativa sistemática
Eric J Bennett1, John Rush, Steven P Gygi
1Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Cell
|December 15, 2010
Resumen
Este estudio revela que la organización de la red de la ubiquitina ligasa (CRL) de cullin-RING está impulsada principalmente por la abundancia del módulo adaptador, no por la nedilación o los ciclos de unión CAND1. La proteómica cuantitativa desafía los modelos existentes de remodelación compleja de los LCR.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
- La proteómica es la proteómica.
Sus antecedentes:
- La reorganización del sistema de señalización es común durante las perturbaciones de la vía.
- Los estudios cuantitativos sobre la remodelación de la red por estímulos de la vía son escasos.
- Los complejos Cullin-RING de ubiquitina ligasa (CRL) son fundamentales para la regulación celular.
Objetivo del estudio:
- Desarrollar una plataforma de proteómica cuantitativa para elucidar la arquitectura de la red de CRL.
- Evaluar los modelos actuales de remodelación dinámica de los LCR.
- Investigar el papel de la nedilación y la unión a CAND1 en la regulación compleja de los LCR.
Principales métodos:
- Desarrollo de una plataforma de proteómica cuantitativa utilizando tecnología de cuantificación absoluta múltiple (AQUA).
- Inhibición aguda de los complejos de CRL utilizando MLN4924, un inhibidor de la enzima activadora de NEDD8.
- Análisis de la estequiometría compleja del LCR y la asociación de subunidades.
Principales resultados:
- La inhibición aguda de los LCR no indujo una reorganización de la red global de LCR.
- Una proporción significativa de las cullinas se ensamblan con módulos de adaptador, independientemente del estado de nedilación.
- Se encontró que solo una pequeña fracción de cullines estaba asociada con CAND1.
Conclusiones:
- La abundancia de módulos de adaptador, en lugar de ciclos de enlace de nedilación / CAND1, parece ser el principal impulsor de la organización de la red de CRL.
- Los modelos actuales de dinámica compleja de los LCR requieren una revisión.
- La proteómica cuantitativa ofrece nuevos conocimientos sobre la compleja regulación de las redes celulares.
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