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DNA-PKcs-PIDDosome: un complejo de activación nuclear de la caspasa-2 con un papel en el mantenimiento del punto de
Mingan Shi1, Carolyn J Vivian, Kyung-Jong Lee
1Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
Cell
|February 11, 2009
Resumen
La activación de la caspasa-2 nuclear (CASP2) está regulada por el daño del ADN. Se forma un nuevo complejo de ADN-PKcs-PIDDosome, fosforilación y activación de CASP2 para mantener los puntos de control y reparación de daños en el ADN.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología molecular La biología molecular.
- La bioquímica es la bioquímica.
Sus antecedentes:
- La caspasa-2 (CASP2) está localizada exclusivamente en el núcleo celular, pero su función allí no está clara.
- Las vías de respuesta al daño del ADN son críticas para mantener la estabilidad genómica.
Objetivo del estudio:
- Para investigar el significado funcional de la localización de la caspasa-2 nuclear.
- Para dilucidar el mecanismo de activación de la caspasa-2 en respuesta al daño del ADN.
Principales métodos:
- La radiación gamma para inducir el daño del ADN.
- Western blotting y inmunoprecipitación para detectar la fosforilación de proteínas y la formación de complejos.
- Análisis celulares para evaluar el punto de control y la reparación del daño en el ADN.
Principales resultados:
- El daño en el ADN desencadena la fosforilación de la caspasa-2 nuclear en S122 por el ADN-PKcs.
- Formación del complejo nuclear ADN-PKcs-PIDDosome, que incluye caspase-2, PIDD y ADN-PKcs.
- La activación de la caspasa-2 es esencial para el mantenimiento del punto de control de daño del ADN G2/M y la reparación del ADN NHEJ.
Conclusiones:
- El ADN-PKcs-PIDDosome es un nuevo complejo nuclear que activa la caspasa-2 en respuesta al daño del ADN.
- La caspasa-2 nuclear juega un papel crítico en las vías de respuesta al daño del ADN, incluido el control y la reparación de los puntos de control.
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