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BID, BIM y PUMA son esenciales para la activación del programa de muerte celular dependiente de BAX y BAK
Decheng Ren1, Ho-Chou Tu, Hyungjin Kim
1Molecular Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Science (New York, N.Y.)
|December 4, 2010
Resumen
Las proteínas BID, BIM y PUMA son esenciales para activar BAX y BAK, proteínas clave para iniciar la apoptosis. Su ausencia en los ratones knockout refleja las deficiencias de Bax y Bak, previniendo la señalización de la muerte celular.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- Genética La genética.
Sus antecedentes:
- El inicio de la apoptosis mitocondrial depende de las proteínas BAX y BAK.
- Los mecanismos precisos de activación de BAX y BAK siguen sin estar claros.
Objetivo del estudio:
- Investigar el papel in vivo de BID, BIM y PUMA en la activación de BAX y BAK.
- Para dilucidar los activadores aguas arriba de BAX y BAK en la apoptosis.
Principales métodos:
- Utilizando ratones de triple nocaut que carecen de Bid, Bim y Puma.
- Analizando los defectos del desarrollo y las vías de señalización de la apoptosis en modelos de knockout.
- Evaluación de la homooligomerización de BAX y BAK y la activación de la caspasa.
Principales resultados:
- Los ratones Bid, Bim y Puma exhibieron defectos de desarrollo similares a las deficiencias de Bax y Bak.
- La deleción genética de BID, BIM y PUMA inhibió la homooligomerización de BAX y BAK.
- La activación de la caspasa mediada por el citocromo c se impidió en estas células knockout a pesar de que otras proteínas BH3-sólo estaban presentes.
Conclusiones:
- BID, BIM y PUMA activan directamente BAX y BAK en las mitocondrias.
- Estas proteínas son cruciales para iniciar la apoptosis en respuesta a varias señales de muerte.
- Muchas formas de apoptosis dependen de la activación mitocondrial directa de BAX y BAK por las proteínas de las familias BID, BIM o PUMA.
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