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Apoptosis de las células T mediada por la liberación inducida por Ca2+ del factor de transcripción MEF2
1Center for Cancer Research, Department of Biology, Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Science (New York, N.Y.)
|October 26, 1999
Resumen
La señalización de calcio activa el factor de transcripción MEF2 a través de Cabin1 y calmodulina, controlando la expresión de Nur77 y la apoptosis de las células T después de la participación del receptor de células T.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología Molecular Biología Molecular
- La señalización celular de las células.
Sus antecedentes:
- La señalización del receptor de células T (TCR) induce la apoptosis del timocito, que implica la expresión génica dependiente del calcio.
- Nur77 y Nor1 son receptores esteroides clave en este proceso, con la expresión de Nur77 regulada por el factor 2 potenciador de miocitos (MEF2).
- El mecanismo preciso que vincula la señalización del calcio a la activación del MEF2 no estaba claro.
Objetivo del estudio:
- Para dilucidar la vía de señalización que conecta el compromiso de TCR, la afluencia de calcio y la activación de MEF2 que conduce a la expresión de Nur77.
- Investigar el papel de Cabin1 y calmodulina en la regulación de la actividad MEF2 durante la apoptosis de células T.
Principales métodos:
- Investigó la interacción entre Cabin1, MEF2 y calmodulina en respuesta a la estimulación de TCR.
- Se analizaron los cambios en la concentración de calcio intracelular y su efecto en la formación de complejos proteicos.
Principales resultados:
- MEF2 es secuestrado por Cabin1 en un estado inactivo.
- El compromiso de la TCR aumenta el calcio intracelular, lo que lleva a la unión de la calmodulina a Cabin1.
- Esta vinculación competitiva libera MEF2, lo que permite su activación y la posterior actividad de promotor de Nur77.
Conclusiones:
- Una nueva vía de señalización que involucra a Cabin1, MEF2 y calmodulina media la expresión de Nur77 inducida por TCR.
- Esta vía es crucial para regular la apoptosis de las células T.
- Los hallazgos proporcionan nuevos conocimientos sobre los mecanismos moleculares de la selección de timocitos.
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