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ABIN-1 es un sensor de ubiquitina que restringe la muerte celular y sostiene el desarrollo embrionario
Shigeru Oshima1, Emre E Turer, Joseph A Callahan
1Department of Medicine, University of California at San Francisco, 513 Parnassus Avenue, S-1057, San Francisco, California 94143-0451, USA.
Nature
|December 9, 2008
Resumen
La deficiencia de la proteína ABIN-1 causa la muerte embrionaria al aumentar la sensibilidad a la muerte celular inducida por el factor de necrosis tumoral (TNF). El ABIN-1 también es conocido como ABIN-1.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Inmunología Inmunología.
- Biología del desarrollo Biología del desarrollo.
Sus antecedentes:
- Las proteínas de señalización del receptor del factor de necrosis tumoral (TNFR) son cruciales para la activación celular y la supervivencia.
- ABIN-1 (conectante A20 e inhibidor de NF-kappaB) es una proteína implicada en la inhibición de la señalización de NF-kappaB.
Objetivo del estudio:
- Investigar la función in vivo de ABIN-1 en el desarrollo embrionario y la supervivencia celular.
- Para dilucidar el mecanismo por el cual ABIN-1 regula la muerte celular programada inducida por el factor de necrosis tumoral (TNF).
Principales métodos:
- Generación y análisis de ratones con deficiencia de ABIN-1.
- Evaluación de la sensibilidad celular a la apoptosis inducida por el TNF.
- Investigación del papel de ABIN-1 en los complejos de señalización del TNF y el reclutamiento de caspasa 8.
- Análisis de la interacción de ABIN-1 con las cadenas de poliubiquitina.
Principales resultados:
- Los ratones con deficiencia de ABIN-1 muestran letalidad embrionaria debido a la apoptosis hepática fetal, la anemia y la hipoplasia.
- Las células deficientes de ABIN-1 muestran hipersensibilidad a la muerte celular programada inducida por TNF, que es rescatada por la deficiencia de TNF.
- ABIN-1 inhibe el reclutamiento de la caspasa 8 a la FADD en los complejos de señalización del TNF, previniendo la apoptosis.
- La actividad antiapoptótica de ABIN-1 depende de su capacidad para unirse a las cadenas de poliubiquitina.
Conclusiones:
- La ABIN-1 es esencial para la supervivencia embrionaria, ya que regula la apoptosis inducida por el TNF.
- ABIN-1 actúa impidiendo la activación de la caspasa 8 a través de la unión de la poliubiquitina.
- Estos hallazgos resaltan el papel crítico de la ubiquitinación y la detección de ubiquitina en la supervivencia de los organismos.
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