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Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
Published on: May 1, 2020
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Requisitos diferenciales para la dosis de eIF4E en el desarrollo normal y el cáncer.
Morgan L Truitt1, Crystal S Conn1, Zhen Shi2
1Department of Urology, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Cell
|June 23, 2015
Resumen
Una reducción del 50% en el factor de iniciación eucariota 4E (eIF4E) impide la transformación de las células cancerosas al limitar la traducción de ARNm específicos. Las células cancerosas secuestran el exceso de eIF4E para la tumorigénesis.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología del cáncer Biología del cáncer.
- Genética La genética.
Sus antecedentes:
- El factor de iniciación eucariota 4E (eIF4E) es la proteína primaria de unión de la capa.
- Su papel en la dosis de traducción orgánica no se ha entendido completamente.
- eIF4E está implicado en el desarrollo del cáncer.
Objetivo del estudio:
- Para investigar el requisito del organismo para la dosificación de eIF4E.
- Comprender el papel de los niveles de eIF4E en la transformación celular y la tumorigénesis.
Principales métodos:
- Generación de un modelo de ratón con haploinsufficiencia Eif4e.
- Perfilado traslacional de todo el genoma.
- Análisis de la traducción del ARNm durante la transformación oncogénica.
Principales resultados:
- Una reducción del 50% en eIF4E (haploinsufficiencia) no afectó el desarrollo normal o la síntesis global de proteínas.
- La reducción de eIF4E afectó significativamente la transformación celular.
- La dosis de eIF4E es crítica para la traducción de ARNm con UTRs 5' específicos involucrados en la regulación de las especies reactivas de oxígeno.
- Este programa de traslación alimenta la supervivencia de las células cancerosas in vivo.
Conclusiones:
- Los niveles de eIF4E son excesivos para el desarrollo normal.
- Las células cancerosas explotan el eIF4E elevado para impulsar un programa de traducción que apoya la tumorigénesis.
- La dosificación dirigida de eIF4E presenta una estrategia terapéutica potencial para el cáncer.
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