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E2f1-3 cambia de activadores en las células progenitoras a represores en las células diferenciadoras
Jean-Leon Chong1, Pamela L Wenzel, M Teresa Sáenz-Robles
1Department of Molecular Virology, Immunology and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
Nature
|December 18, 2009
Resumen
La proteína del retinoblastoma (Rb) y los activadores E2f (E2f1-3) tienen una doble función en el control del ciclo celular. E2f1-3 son vitales para la supervivencia de las células progenitoras, no para la división, y reprimen la diferenciación.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- Genética La genética.
Sus antecedentes:
- La proteína del retinoblastoma (Rb) inhibe tradicionalmente la progresión del ciclo celular mediante el secuestro de los activadores E2f (E2f1-3).
- E2f1-3 se consideran efectores clave que impulsan a las células a la fase S y la proliferación.
Objetivo del estudio:
- Investigar las funciones in vivo de E2f1, E2f2 y E2f3 en el control del ciclo celular de mamíferos.
- Para aclarar las funciones dependientes del contexto de E2f1-3 como activadores versus represores.
Principales métodos:
- Se utilizaron ratones cre-transgénicos específicos del tejido y alelos E2f condicionales.
- Examinó la triple deficiencia E2f1-3 en células madre embrionarias murinas, embriones e intestinos delgados.
Principales resultados:
- En la división de las células progenitoras, E2f1-3 actúan como activadores, pero son indispensables para la división, crucial para la supervivencia.
- En las células que se diferencian, el complejo E2f1-3 con Rb reprime los objetivos E2f y promueve la salida del ciclo celular.
- La inactivación de Rb en las células diferenciadoras cambió E2f1-3 a activadores, causando divisiones ectópicas; la pérdida de E2f1-3 rescató esto.
Conclusiones:
- E2f1-3 funciona dinámicamente como activadores o represores dependiendo del contexto celular (división versus diferenciación).
- E2f1-3 son esenciales para la supervivencia de las células progenitoras y juegan un papel crítico en la salida del ciclo celular durante la diferenciación.
- Este estudio redefine las funciones de E2f1-3 en ciclos celulares normales y aberrantes, lo que tiene un impacto en la investigación del cáncer.
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