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Menin interactúa con el factor de transcripción AP1 JunD y reprime la transcripción activada por JunD

S K Agarwal¹, S C Guru, C Heppner

¹Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. sunitaa@amb.niddk.nih.gov

|February 16, 1999

Resumen

El supresor tumoral menin (del gen MEN1) se une directamente al factor de transcripción JunD. Esta interacción inhibe el JunD.

Área de la Ciencia:

Biología Molecular Biología Molecular
Genética La genética.
Investigación del cáncer Investigación del cáncer.

Sus antecedentes:

El gen supresor de tumores MEN1 codifica el menin, una proteína nuclear con una función no caracterizada.
Comprender las interacciones moleculares del menin es crucial para elucidar su papel en la supresión de tumores.

Objetivo del estudio:

Para identificar las proteínas que interactúan con el menin.
Para investigar las consecuencias funcionales de la interacción menin-JunD.

Principales métodos:

Cribado de dos híbridos de levadura para identificar socios que interactúan entre sí.
Ensayos in vitro e in vivo para confirmar las interacciones de las proteínas.
Los ensayos del gen reportero evalúan la actividad transcripcional.

Principales resultados:

Identificó el factor de transcripción JunD como un socio directo de unión al meni.
Se confirmó la interacción menin-JunD utilizando múltiples enfoques experimentales.
Se ha demostrado que el menin reprime la activación transcripcional mediada por JunD.
Se demostró que las mutaciones de MEN1 interrumpen la interacción del menin con JunD.

Conclusiones:

La actividad supresora de tumores de Menin está mediada a través de la unión directa a JunD.
La inhibición de la transcripción activada por JunD es un mecanismo clave de la función supresora de tumores del menin.
La interacción menin-JunD es crítica para el papel de MEN1 en la prevención del desarrollo de tumores.

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