Cascada de señalización AMPK-SKP2-CARM1 en la regulación transcripcional de la autofagia
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Hi-Jai R Shin1, Hyunkyung Kim1, Sungryong Oh1
1Creative Research Initiatives Center for Chromatin Dynamics, School of Biological Sciences, Seoul National University, Seoul, South Korea.
Nature
|June 17, 2016
Resumen
La arginina metiltransferasa asociada al coactivador 1 (CARM1) es vital para la autofagia. El hambre de nutrientes activa un eje de señalización que aumenta el CARM1, promoviendo la metilación de histonas y la expresión génica de la autofagia.
Área de la Ciencia:
- Biología celular
- Biología molecular
- La epigenética
Sus antecedentes:
- La autofagia es crucial para la homeostasis celular, particularmente durante el hambre de nutrientes.
- La regulación transcripcional y epigenética de la autofagia sigue siendo incompletamente entendida.
- El papel de CARM1 en la autofagia no se ha establecido previamente.
Objetivo del estudio:
- Para investigar el papel de CARM1 en la autofagia de los mamíferos.
- Esclarecer los mecanismos moleculares que regulan la estabilidad y la función de CARM1 en la autofagia.
- Identificar nuevas vías de señalización involucradas en la inducción de la autofagia.
Principales métodos:
- Se estudió la regulación de la estabilidad de CARM1 por la ubiquitina ligasa SCF E3.
- Se investigó el efecto de la inanición de nutrientes en la fosforilación de FOXO3a por AMPK.
- Se realizaron análisis de todo el genoma para identificar los genes diana de CARM1.
Principales resultados:
- La estabilidad de CARM1 está regulada por SKP2 en el núcleo bajo condiciones ricas en nutrientes.
- El hambre de nutrientes conduce a la fosforilación FOXO3a dependiente de AMPK, reprimiendo SKP2 y aumentando CARM1.
- CARM1 mejora la expresión génica de la autofagia a través de la metilación de histonas y la interacción con TFEB.
Conclusiones:
- CARM1 es un componente nuclear clave en la regulación de la autofagia.
- Un nuevo eje de señalización (AMPK-SKP2-CARM1) controla la inducción de la autofagia.
- La metilación de la histona arginina dependiente de CARM1 es crítica para la autofagia.
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