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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
La fosfatasa PAC1 es un objetivo de transcripción de p53 en la señalización de la apoptosis y la supresión del
Yuxin Yin1, Yu-Xin Liu, Yan J Jin
1Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, New York 10032, USA.
Nature
|April 4, 2003
Resumen
El supresor tumoral p53 activa la fosfatasa PAC1 (fosfatasa de doble especificidad 2) durante la apoptosis. PAC1 es esencial para la apoptosis mediada por p53 y la supresión tumoral, revelando un nuevo mecanismo de regulación génica.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
- Investigación del cáncer Investigación del cáncer.
Sus antecedentes:
- La proteína supresora de tumores p53 regula los procesos celulares a través del control transcripcional de los genes objetivo.
- PAC1 (fosfatasa de células activadas 1), también conocida como DUSP2, es una fosfatasa dual que inactiva las cinasas MAP.
Objetivo del estudio:
- Para investigar el papel de p53 en la regulación de la transcripción de PAC1.
- Para dilucidar el mecanismo de la apoptosis mediada por p53 que involucra al PAC1.
- Para explorar la función de PAC1 en la supresión de tumores.
Principales métodos:
- Análisis de la actividad del promotor PAC1 y la unión p53.
- Uso de ARN pequeño interferente (siRNA) para reducir la expresión de PAC1.
- Estudios de sobreexpresión de PAC1.
- Medición de la actividad de la MAP quinasa.
Principales resultados:
- p53 activa directamente la transcripción de PAC1 al unirse a un sitio palíndromo en su promotor.
- La inducción de PAC1 por p53 ocurre bajo privación sérica y estrés oxidativo, lo que lleva a la apoptosis.
- La reducción mediada por siRNA de PAC1 inhibe la apoptosis inducida por p53, mientras que la sobreexpresión de PAC1 aumenta la apoptosis y suprime la formación de tumores.
- La activación de p53 inhibe la actividad de la MAP quinasa, y PAC1 es necesaria y suficiente para este proceso.
Conclusiones:
- p53 regula la transcripción de PAC1 a través de un nuevo sitio de unión bajo condiciones de estrés específicas.
- PAC1 es un mediador clave de la apoptosis dependiente de p53 y la supresión tumoral.
- La identificación de un sitio palíndromo de unión a p53 ofrece información sobre los mecanismos de regulación genética de p53.
Palabras clave:
No programático No programático
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