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SREBP-1, una proteína de cremallera básica-hélice-bucle-hélice-leucina que controla la transcripción del gen receptor
C Yokoyama1, X Wang, M R Briggs
1Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
Cell
|October 8, 1993
Resumen
Los investigadores clonaron la proteína-1 de unión al elemento regulador del esterol humano (SREBP-1), un regulador clave de la transcripción génica del receptor de lipoproteínas de baja densidad (LDL). Esta proteína es la proteína
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Genética La genética.
- La bioquímica es la bioquímica.
Sus antecedentes:
- El elemento regulador de esteroles 1 (SRE-1) controla la transcripción del gen del receptor de lipoproteínas de baja densidad (LDL), respondiendo a los niveles de esteroles celulares.
- SRE-1 se activa en las células empobrecidas de esteroles y se silencia por los esteroles, lo que indica un mecanismo regulador crítico en el metabolismo del colesterol.
Objetivo del estudio:
- Para clonar el cDNA de la proteína humana que se une a SRE-1 y media la regulación de esteroles.
- Caracterizar la estructura y función de este nuevo factor de transcripción, identificado como SREBP-1.
Principales métodos:
- clonación de ADNc de SREBP-1 humano.
- Análisis del motivo de la cremallera básica-hélice-bucle-hélice-leucina (bHLH-ZIP) y la secuencia de ADN objetivo.
- Los ensayos del gen reportero evalúan la activación transcripcional por SREBP-1 en presencia y ausencia de esteroles.
Principales resultados:
- Se clonó el cDNA SREBP-1 humano, revelando una gran proteína (1147 aminoácidos) con un motivo bHLH-ZIP.
- SREBP-1 se une a SRE-1, una repetición directa de CAC, que difiere de los sitios de unión bHLH-ZIP canónicos.
- La sobreexpresión de SREBP-1 activó robustamente la transcripción del gen reportero, independientemente de los niveles de esterol, aboliendo la regulación mediada por esterol.
Conclusiones:
- SREBP-1 se identifica como la proteína que media en la etapa reguladora final en el metabolismo de LDL al unirse a SRE-1.
- El motivo de unión único y la potente actividad sugieren que la SREBP-1 está regulada por un factor desconocido.
- Comprender la regulación de SREBP-1 es crucial para controlar los niveles de colesterol en el plasma en humanos.
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