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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
El supresor tumoral HIC1 regula directamente SIRT1 para modular las respuestas de daño al ADN dependientes de p53
Wen Yong Chen1, David H Wang, Raywhay Chiu Yen
1Cancer Biology Program, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University, Baltimore, Maryland 21231, USA.
Cell
|November 5, 2005
Resumen
La pérdida de la función hipermetilada en el cáncer 1 (HIC1) activa la SIRT1, que inactiva la p53, promoviendo el desarrollo del cáncer. Este silenciamiento epigenético de HIC1 durante el envejecimiento aumenta el riesgo de cáncer.
Área de la Ciencia:
- La epigenética es la epigenética.
- Biología del cáncer Biología del cáncer.
- Mecanismos moleculares del envejecimiento.
Sus antecedentes:
- El hipermetilado en el cáncer 1 (HIC1) es un represor transcripcional epigenéticamente regulado.
- HIC1 coopera con p53 para suprimir el desarrollo de cáncer dependiente de la edad en ratones.
Objetivo del estudio:
- Para aclarar el mecanismo por el cual la pérdida de HIC1 promueve la tumorigénesis.
- Para investigar el papel de SIRT1 en la supresión del cáncer mediada por HIC1.
Principales métodos:
- Análisis de la interacción HIC1-SIRT1 y la regulación transcripcional.
- Evaluación de la función de p53 y la apoptosis en células con diferentes niveles de HIC1 y SIRT1.
- Investigación del silenciamiento epigenético de HIC1 durante el envejecimiento.
Principales resultados:
- HIC1 forma un complejo con SIRT1, reprimiendo la transcripción de SIRT1.
- La inactivación de HIC1 conduce a un aumento de la expresión de SIRT1, que inactiva p53.
- La inhibición de SIRT1 restaura la sensibilidad a la apoptosis en las células deficientes de HIC1.
- La hipermetilación y el silenciamiento HIC1 asociados con el envejecimiento se correlacionan con la regulación al alza de SIRT1.
Conclusiones:
- La pérdida de HIC1 promueve el cáncer mediante la regulación al alza de SIRT1, atenuando así la función de p53.
- La regulación al alza de SIRT1 debido al silenciamiento de HIC1 puede contribuir tanto a la supervivencia celular del envejecimiento como al aumento del riesgo de cáncer.
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