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TOR regula la expresión génica de la proteína ribosómica a través de PKA y el factor de transcripción FHL1 de

Dietmar E Martin¹, Alexandre Soulard, Michael N Hall

¹Division of Biochemistry, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.

|December 29, 2004

Resumen

El objetivo de la vía de la rapamicina (TOR) regula la biogénesis del ribosoma a través de la proteína quinasa A (PKA). Este estudio identifica el factor de transcripción tipo garfo 1 (FHL1) y sus cofactores IFH1 y CRF1 como actores clave en este mecanismo de señalización sensible a los nutrientes.

Área de la Ciencia:

Biología celular Biología celular.
Biología Molecular Biología Molecular
La bioquímica es la bioquímica.

Sus antecedentes:

La biogénesis del ribosoma es crucial para el crecimiento celular y está estrictamente regulada por las señales ambientales.
El objetivo sensible a los nutrientes de la vía de señalización de la rapamicina (TOR) es un regulador central del crecimiento celular.
TOR influye en la localización de la proteína quinasa A (PKA), pero sus factores de transcripción aguas abajo para la regulación génica de la proteína ribosómica (RP) siguen sin identificarse.

Objetivo del estudio:

Para dilucidar los factores de transcripción que median la regulación del gen RP por la vía TOR-PKA en la levadura.
Descubrir el mecanismo de señalización que vincula la detección ambiental con el control de la biogénesis ribosómica.

Principales métodos:

Genética de la levadura y técnicas de biología molecular.
Análisis de la localización y actividad del factor de transcripción.
Investigación de las interacciones proteína-proteína en los promotores del gen RP.

Principales resultados:

El factor de transcripción FHL1, junto con el coactivador IFH1 y el corepresor CRF1, son esenciales para la transcripción del gen RP mediada por TOR/PKA.
La señalización TOR, a través de PKA, inhibe la actividad de la quinasa YAK1 y retiene CRF1 en el citoplasma.
La inactivación de TOR conduce a la activación de YAK1, la fosforilación de CRF1, la acumulación nuclear y la posterior inhibición de la transcripción del gen RP al competir con IFH1 para la unión de FHL1.

Conclusiones:

Se describe una nueva vía de señalización, que conecta la detección ambiental a través de TOR / PKA a la regulación de la biogénesis del ribosoma.
La interacción entre FHL1, IFH1, CRF1 y YAK1 proporciona un mecanismo para controlar la expresión génica de RP en respuesta a la disponibilidad de nutrientes.

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