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Interacción entre la proteína ATM y c-Abl en respuesta al daño del ADN
T Shafman1, K K Khanna, P Kedar
1Joint Center for Radiation Therapy, Dana Farber Cancer Institutes, Boston, Massachusetts 02115, USA.
Nature
|May 29, 1997
Resumen
La proteína Ataxia telangiectasia mutada (ATM) interactúa con la c-Abl tirosina quinasa en respuesta al daño del ADN. Esta interacción es crucial para activar c-Abl y mediar la detención del ciclo celular G1/S después de la exposición a la radiación.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
- Genética La genética.
Sus antecedentes:
- La ataxia telangiectasia (AT) es un trastorno autosómico recesivo causado por mutaciones en el gen ATM.
- ATM es una enzima similar a la fosfatidilinositol-3-cinasa involucrada en la respuesta al daño del ADN y el control del ciclo celular.
- Las células AT muestran hipersensibilidad a la radiación ionizante y defectos en el punto de control G1/S.
Objetivo del estudio:
- Investigar la posible interacción entre ATM y c-Abl en respuesta al daño del ADN.
- Para aclarar el papel de ATM en la activación de la actividad de la c-Abl tirosina quinasa.
Principales métodos:
- Investigó la unión de ATM y c-Abl en las células de control y AT.
- Identificó el motivo específico de interacción entre ATM y c-Abl utilizando ensayos de unión a proteínas.
- Evaluó el efecto del daño del ADN en la actividad de la c-Abl tirosina quinasa en las células AT.
Principales resultados:
- ATM se une constitutivamente a c-Abl en las células normales, pero esta interacción está ausente en las células AT.
- El dominio SH3 de c-Abl interactúa con un motivo específico (DPAPNPPHFP) en ATM.
- La activación inducida por radiación de la c-Abl tirosina quinasa se reduce significativamente en las células AT.
Conclusiones:
- ATM juega un papel crítico en la activación inducida por daño al ADN de c-Abl.
- La interacción entre ATM y c-Abl es esencial para mediar la detención del ciclo celular G1/S inducida por la radiación.
- Estos hallazgos revelan un nuevo mecanismo en las vías de respuesta al daño del ADN.
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