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Un papel esencial de la arginilación N-terminal en el desarrollo cardiovascular
Yong Tae Kwon1, Anna S Kashina, Ilia V Davydov
1Division of Biology, 147-75, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
Science (New York, N.Y.)
|July 6, 2002
Resumen
El gen Arg-tRNA-proteína transferasa (R-transferasa) ATE1 es crucial para el desarrollo embrionario, particularmente la formación del corazón. Su vía de arginilación actúa como un sensor de oxígeno, con cisteína oxidada que precede a la arginilación.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
- Biología del desarrollo Biología del desarrollo.
Sus antecedentes:
- La vía de la regla N-terminal regula la degradación de las proteínas a través de los aminoácidos N-terminales.
- La arginilación, mediada por las transferasas de la proteína Arg-tRNA (R-transferasas), se dirige a residuos N-terminales específicos como el aspartato, el glutamato y la cisteína.
- El gen ATE1 codifica estas R-transferasas en los mamíferos.
Objetivo del estudio:
- Para investigar la función del gen ATE1 en el desarrollo de los mamíferos.
- Para aclarar el papel de la arginilación N-terminal en la degradación de las proteínas y los procesos celulares.
- Para determinar si la vía de arginilación funciona como un sensor de oxígeno.
Principales métodos:
- Generación de cepas de ratón que carecen de ATE1 (ATE1-/-)
- Análisis fenotípico de embriones ATE1-/-, centrado en el desarrollo del corazón y la remodelación vascular.
- Ensayos bioquímicos para estudiar el mecanismo de arginilación N-terminal, incluida la oxidación del sustrato.
Principales resultados:
- Los embriones ATE1-/- exhiben letalidad embrionaria debido a defectos graves en el desarrollo del corazón y la remodelación angiogénica.
- Los análisis bioquímicos revelan que la cisteína N-terminal se oxida antes de la arginilación.
- Esta arginilación dependiente de la oxidación contrasta con la arginilación directa del aspartato y el glutamato N-terminales.
Conclusiones:
- El gen ATE1 y sus R-transferasas codificadas son esenciales para la supervivencia embrionaria, el desarrollo del corazón y la formación vascular.
- La arginilación de la cisteína N-terminal, que implica una oxidación previa, sugiere un nuevo mecanismo regulador.
- La rama de arginilación de la vía de la regla N-end probablemente funcione como un sensor de oxígeno biológico.
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