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La destrucción dependiente de feromonas del factor de transcripción Tec1 es necesaria para la especificidad de

Marie Z Bao¹, Monica A Schwartz, Greg T Cantin

¹Department of Biochemistry and Biophysics, University of California, 600 16th Street, San Francisco, CA 94143, USA.

|December 29, 2004

Resumen

Las células de levadura usan Fus3 para degradar la proteína Tec1, impidiendo que las señales de apareamiento activen el crecimiento filamentoso. Esto asegura distintas funciones de las vías celulares a través de la destrucción de proteínas dirigidas.

Área de la Ciencia:

Las vías de señalización celular.
Mecanismos moleculares de la regulación génica.
Genética de la levadura y biología celular.

Sus antecedentes:

Las vías MAPK de la levadura para el apareamiento y el crecimiento filamentoso comparten componentes, pero tienen resultados distintos.
El MAPK específico para el apareamiento, Fus3, normalmente impide el cruce de vías a través de mecanismos desconocidos.

Objetivo del estudio:

Para dilucidar el mecanismo por el cual Fus3 evita el cruce entre el apareamiento de la levadura y las vías de crecimiento filamentoso.
Para identificar los actores moleculares involucrados en el mantenimiento de la especificidad de la señalización.

Principales métodos:

Se ha investigado la degradación dependiente de Fus3 del factor de transcripción de la filamentación, Tec1.
Genética de levadura utilizada, incluidas las deleciones de genes y mutaciones puntuales (por ejemplo, Tec1 T273A).
Interacciones proteína-proteína examinadas y ensayos in vitro de quinasa que involucran a Fus3 y Tec1.
Se evaluó el papel de los componentes de la ubiquitina ligasa del SCF (Dia2, Cdc53) en la degradación de Tec1.

Principales resultados:

La señalización de feromonas induce la degradación dependiente de Fus3 de Tec1.
La degradación de Tec1 requiere actividad de Fus3 quinasa y fosforilación en Threonine 273.
Fus3 directamente fosforila el Tec1 en el T273.3.
La destrucción de Tec1 está mediada por el complejo de ligasa de ubiquitina SCF, que involucra a Dia2 y Cdc53.3.
Las mutaciones que interrumpen la fosforilación Tec1 o la función Fus3/Dia2 conducen a la pérdida de la especificidad de la señalización, activando los genes de filamentación durante el apareamiento.

Conclusiones:

La destrucción inducida por la señal de un factor de transcripción de una vía competidora (Tec1) por Fus3 es un mecanismo clave para garantizar la especificidad de la vía MAPK de la levadura.
Este proceso evita la activación inapropiada de los genes de crecimiento filamentoso durante el apareamiento.

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