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High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes
Published on: March 3, 2015
La vía de señalización TOR controla la localización nuclear de los factores de transcripción regulados por los
Nature
|December 22, 1999
Resumen
La vía de señalización TOR en la levadura controla el metabolismo de los nutrientes manteniendo los factores clave de transcripción en el citoplasma. Este mecanismo impide la expresión de genes relacionados con el hambre y la regulación de las fuentes de carbono.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- La bioquímica es la bioquímica.
Sus antecedentes:
- La vía de señalización Target of Rapamycin (TOR) regula el crecimiento celular en respuesta a nutrientes como el nitrógeno y el carbono en Saccharomyces cerevisiae.
- Las quinasas TOR (TOR1 y TOR2) manejan la síntesis y degradación de proteínas a través de TAP42, pero su papel en los eventos nucleares, específicamente la represión de la transcripción inducida por el hambre, sigue sin estar claro.
Objetivo del estudio:
- Aclarar el mecanismo por el cual la vía de señalización TOR controla los eventos nucleares, en particular la represión de la transcripción específica de la inanición.
- Investigar cómo la señalización TOR influye en la expresión de genes regulados por la disponibilidad de nitrógeno y carbono.
Principales métodos:
- Investigó la interacción entre GLN3 y URE2 mediada por la fosforilación dependiente de TOR.
- Se analizó el papel de TAP42 y la fosfatasa SIT4 en la fosforilación de GLN3 y la retención citoplasmática.
- Se examinó la unión de MSN2 y MSN4 a BMH2, un proceso dependiente de TOR.
Principales resultados:
- La señalización TOR promueve la asociación del factor de transcripción GATA GLN3 con URE2, lo que requiere una fosforilación GLN3 dependiente de TOR.
- La fosforilación de GLN3 y la localización en el citoplasma dependen del efector TOR TAP42 y se oponen a la fosfatasa SIT4.
- La señalización TOR inhibe los genes regulados por la fuente de carbono al mejorar la unión de los activadores transcripcionales MSN2 y MSN4 a la proteína citoplasmática BMH2.
Conclusiones:
- La vía de señalización TOR regula ampliamente el metabolismo de los nutrientes mediante el secuestro de múltiples factores de transcripción, incluidos GLN3, MSN2 y MSN4, en el citoplasma.
- Este secuestro citoplasmático por TOR impide la transcripción de genes asociados con la limitación de nutrientes y fuentes específicas de carbono.
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