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In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
Published on: July 25, 2019
Mono- versus poliubiquitinación: control diferencial del destino de p53 por medio de Mdm2
Muyang Li1, Christopher L Brooks, Foon Wu-Baer
1Institute for Cancer Genetics and Department of Pathology, College of Physicians & Surgeons, Columbia University, 1150 St. Nicholas Avenue, New York, NY 10032, USA.
Science (New York, N.Y.)
|December 13, 2003
Resumen
Los niveles de proteína Mdm2 dictan el destino de la p53. La baja actividad de Mdm2 causa la exportación nuclear de p53, mientras que el alto Mdm2 promueve la degradación de p53, lo que aclara la ubiquitinación.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- La bioquímica es la bioquímica.
Sus antecedentes:
- La ubiquitinación mediada por Mdm2 es crucial para regular la estabilidad y la localización del supresor tumoral p53.
- No se comprenden completamente los mecanismos moleculares precisos que dictan si Mdm2 se dirige a p53 para la degradación o la exportación nuclear.
Objetivo del estudio:
- Para dilucidar las funciones diferenciales de los niveles de actividad de Mdm2 en la modulación de la ubiquitinación de p53 y la localización subcelular.
- Investigar el impacto específico de la monoubiquitinación de p53 frente a la poliubiquitinación en el tráfico y la degradación de p53.
Principales métodos:
- Análisis del estado de ubiquitinación de p53 bajo diferentes niveles de actividad de Mdm2.
- Investigando la localización subcelular de p53 y sus formas ubiquitinadas.
- Utilizando una proteína de fusión de p53-ubiquitina para imitar la monoubiquitinación.
Principales resultados:
- Los bajos niveles de actividad de Mdm2 resultan en la monoubiquitinación de p53 y la subsiguiente exportación nuclear.
- Los altos niveles de actividad de Mdm2 conducen a la poliubiquitinación y degradación de p53 dentro del núcleo.
- Una proteína de fusión de p53-ubiquitina, que imita la monoubiquitinación, se acumula en el citoplasma independientemente de Mdm2.
Conclusiones:
- La monoubiquitinación de p53 es un determinante crítico para su tráfico citoplasmático.
- Los distintos niveles de actividad de Mdm2 orquestan diferentes vías de ubiquitinación, controlando el destino de la p53.
- Este estudio aclara el papel de la ubiquitinación en la regulación de p53, destacando el control dependiente de la dosis de Mdm2.
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