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Atg7 modula la actividad de p53 para regular el ciclo celular y la supervivencia durante el estrés metabólico
In Hye Lee1, Yoshichika Kawai, Maria M Fergusson
1Center for Molecular Medicine, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA.
Science (New York, N.Y.)
|April 14, 2012
Resumen
El gen de la autofagia Atg7 es crucial para la detención del ciclo celular durante la retirada de nutrientes. Regula la p53, controla la división celular y la apoptosis, previene el daño del ADN y la letalidad en ratones.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- Genética La genética.
Sus antecedentes:
- La retirada de nutrientes desencadena la detención del ciclo celular, la autofagia y la muerte celular.
- La interacción entre estas respuestas al estrés no se entiende completamente.
Objetivo del estudio:
- Investigar el papel del gen de la autofagia Atg7 en las respuestas celulares a la privación de nutrientes.
- Para aclarar la relación entre Atg7, la regulación del ciclo celular y las vías de muerte celular.
Principales métodos:
- Se utilizaron fibroblastos embrionarios de ratón que carecían de Atg7.
- Se analizó la progresión del ciclo celular, la unión a p53, la transcripción p21 ((CDKN1A), el daño al ADN y la apoptosis.
- Se investigó el efecto de la deleción de Chk2 en la supervivencia del ratón Atg7{\displaystyle Atg7{\text{-}}} .
Principales resultados:
- Las células deficientes de Atg7 no pudieron detener el ciclo celular al morir de hambre.
- Atg7 se une directamente a p53, regulando la expresión de p21 ((CDKN1A) independientemente de su actividad enzimática.
- La ausencia de Atg7 condujo a un aumento del daño del ADN y la apoptosis p53-dependiente bajo estrés prolongado.
- La inhibición de la respuesta al daño del ADN rescató parcialmente la letalidad en ratones Atg7 ((-/-)).
Conclusiones:
- Atg7 es esencial para la detención del ciclo celular inducida por la privación de nutrientes.
- Atg7 modula la actividad de p53 para controlar la detención del ciclo celular y la apoptosis.
- Atg7 juega un papel crítico en la gestión de las respuestas de estrés celular a la limitación de nutrientes.
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