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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
La unión y modulación de p53 por los coactivadores p300/CBP
N L Lill1, S R Grossman, D Ginsberg
1The Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Nature
|June 19, 1997
Resumen
Las oncoproteínas virales interrumpen la función de p53 al interferir con la unión p300/CBP. Esta interacción es crucial para el p53.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
- Virología Virología.
Sus antecedentes:
- Las oncoproteínas del antígeno T grande del adenovirus E1A y SV40 interactúan con los coactivadores transcripcionales p300/CBP.
- Esta interacción está vinculada a los mecanismos de transformación celular.
- Una región de unión compartida en el antígeno T sugiere una conexión entre las funciones p53 y p300 / CBP.
Objetivo del estudio:
- Investigar la interacción directa entre p300/CBP y p53.
- Determinar las consecuencias funcionales de esta interacción en los procesos celulares mediados por p53.
- Para aclarar el papel de p300 / CBP como mediador de la actividad de p53.
Principales métodos:
- Los ensayos de coinmunoprecipitación detectan las interacciones proteína-proteína.
- Microscopía de inmunofluorescencia para evaluar la localización subcelular.
- Los ensayos del gen reportero miden la activación del promotor.
- Análisis del ciclo celular y ensayos de apoptosis para evaluar los resultados funcionales.
Principales resultados:
- p300/CBP se une directamente a p53 en ausencia de las oncoproteínas virales.
- p300 y p53 se colocalizan en el núcleo y forman un complejo estable de unión al ADN.
- El adenovirus E1A interrumpe la activación transcripcional mediada por p53 de los promotores p21 y bax.
- E1A suprime la detención del ciclo celular G1 inducida por p53 y la apoptosis.
Conclusiones:
- p300/CBP actúa como un adaptador de transcripción para p53.
- p300/CBP modula el papel de p53 en el control del punto de control del ciclo celular G1 y la inducción de la apoptosis.
- La interrupción del complejo p300/p53 por las oncoproteínas virales contribuye a la transformación celular.
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