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El locus del extintor específico del tejido TSE1 codifica una subunidad reguladora de la proteína quinasa dependiente
1Institute of Cell and Tumor Biology, German Cancer Research Center, Heidelberg.
Cell
|September 6, 1991
Resumen
El locus extintor específico del tejido (TSE1) fue identificado como la subunidad reguladora RI alfa de la proteína quinasa A (PKA). Este hallazgo explica cómo TSE1 reprime la transcripción génica a través de vías de señalización mediadas por CAMP.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Genética La genética.
- La señalización celular.
Sus antecedentes:
- El locus extintor específico del tejido (TSE1) es un regulador de la transcripción en híbridos de células somáticas.
- La TSE1 reprime los potenciadores específicos de los hepatocitos mediante la interacción con los elementos de respuesta cAMP (CRE).
Objetivo del estudio:
- Para identificar la identidad molecular del locus TSE1.
- Para dilucidar el mecanismo de la represión transcripcional mediada por TSE1.
Principales métodos:
- Análisis de la expresión génica y la actividad genética.
- Mapeo de alta resolución de genes en el cromosoma humano 17.
- Estudios funcionales utilizando el cDNA alfa RI transfectado.
Principales resultados:
- La subunidad reguladora RI alfa de la proteína quinasa A (PKA) fue identificada como el producto del locus TSE1.
- Se observó la expresión concordante del ARNm RI alfa y la actividad de TSE1.
- La transfección de RI alfa cDNA imitó la extinción mediada por TSE1.
- TSE1/RI alfa reprime la actividad basal de PKA y la fosforilación de CREB en el Ser-133.
Conclusiones:
- TSE1 es la subunidad reguladora RI alfa de PKA.
- TSE1/RI alfa media la represión transcripcional inhibiendo la actividad de PKA y la señalización aguas abajo.
- Esto identifica un nuevo mecanismo para la regulación génica que involucra a PKA y CREB.
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