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Yeast As a Chassis for Developing Functional Assays to Study Human P53
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La proteína quinasa dependiente del ADN no es necesaria para la respuesta dependiente de p53 al daño del ADN
G S Jimenez1, F Bryntesson, M I Torres-Arzayus
1Gene Expression Laboratory, The Salk Institute, La Jolla, California 92037, USA.
Nature
|July 14, 1999
Resumen
La proteína quinasa dependiente del ADN (ADN-PK) no es necesaria para la activación del supresor tumoral p53 después del daño del ADN. Los estudios muestran que la respuesta p53 permanece funcional en las células que carecen de ADN-PK, desafiando las suposiciones anteriores.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
- Investigación del cáncer Investigación del cáncer.
Sus antecedentes:
- El daño en el ADN desencadena la activación del supresor tumoral p53, crucial para prevenir la inestabilidad genética y el cáncer.
- Se debate el papel de la proteína quinasa dependiente del ADN (ADN-PK) en la activación de p53.
- Comprender la vía de señalización del daño en el ADN-p53 es vital para la investigación del cáncer.
Objetivo del estudio:
- Para investigar la necesidad de ADN-PK en la respuesta al daño del ADN mediada por p53.
- Para aclarar el controvertido papel del ADN-PK en la activación de p53.
Principales métodos:
- Utilizó fibroblastos embrionarios primarios de ratón genéticamente deficientes en el ADN-PK.
- Se evaluó la acumulación de p53, la fosforilación, la localización nuclear y la unión al ADN después de la irradiación.
- Se evaluó la regulación al alza del gen p53 objetivo y la detención del ciclo celular.
Principales resultados:
- El daño al ADN inducido por la irradiación desencadenó una respuesta p53 normal en las células deficientes de ADN-PK.
- Se observó una acumulación normal de p53, fosforilación en la serina 15, translocación nuclear y unión al ADN.
- La upregulación de los genes diana de p53 y la detención del ciclo celular ocurrieron efectivamente sin ADN-PK.
Conclusiones:
- La actividad del ADN-PK no es esencial para una respuesta funcional dependiente de p53 al daño del ADN.
- Una línea celular con deficiencia de ADN-PK previamente estudiada (SCGR11) tenía una mutación p53 confusa.
- Los hallazgos desafían el papel esencial propuesto del ADN-PK en esta vía celular crítica.
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