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Taspase1: una treonina aspartasa requerida para la escisión de MLL y la correcta expresión del gen HOX
James J-D Hsieh1, Emily H-Y Cheng, Stanley J Korsmeyer
1Howard Hughes Medical Institute, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Cell
|November 26, 2003
Resumen
Los investigadores identificaron Taspase1, una proteasa crucial para la escisión de la proteína de la leucemia de linaje mixto (MLL). Esta escisión es esencial para mantener la expresión del gen HOX y el desarrollo adecuado.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Genética La genética.
- La bioquímica es la bioquímica.
Sus antecedentes:
- El gen de la Leucemia de linaje mixto (MLL) es vital para la expresión del gen HOX, homólogo a Drosophila trithorax.
- La proteína MLL se divide en fragmentos N320 y C180, que se heterodimerizan para obtener estabilidad y localización subnuclear.
Objetivo del estudio:
- Identificar y clonar la proteasa responsable de la escisión de la proteína MLL.
- Para caracterizar la función y el origen evolutivo de esta proteasa de división de MLL.
Principales métodos:
- Purificación y clonación de la proteasa de división de MLL.
- Caracterización de la actividad enzimática y estructura de la proteasa.
- Interferencia de ARN (RNAi) para evaluar los efectos de la eliminación de la proteasa en el procesamiento de MLL y la expresión génica HOX.
Principales resultados:
- La proteasa fue identificada como Taspase1, una endopeptidasa que utiliza un nucleófilo de treonina N-terminal.
- Taspase1 se somete a una escisión intramolecular para formar un heterodímero alfa/beta activo.
- Taspase1 knockdown condujo a MLL sin procesar y alteró la expresión del gen HOX.
Conclusiones:
- Taspase1 es esencial para el procesamiento de MLL y la posterior regulación del gen HOX.
- La coevolución de Taspase1 con MLL sugiere su papel en el desarrollo de planes corporales complejos en organismos superiores.
- Taspase1 representa una nueva clase de proteasas que comienzan con una treonina N-terminal.
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