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2024, Número 4

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Rev Educ Bioquimica 2024; 43 (4)


Función y regulación del modulador negativo del ciclo celular Wee1, una visión histórica y avances más recientes

López-Hernández MN, Guerrero-Molina ED, Romero-Rodríguez S, Vázquez-Ramos JM

Idioma: Español
Referencias bibliográficas: 125
Paginas: 245-265
Archivo PDF: 1035.42 Kb.


RESUMEN

Wee1 es una cinasa que regula negativamente la progresión del ciclo celular mediante la fosforilación de un residuo de tirosina altamente conservado en las cinasas dependientes de ciclina (CDKs), cuya actividad es necesaria para la progresión del ciclo celular. Wee1 se descubrió hace más de 50 años en levaduras de fisión, cuando mutantes en el gen mostraron células con un fenotipo pequeñito (wee), ya que éstas avanzaron prematuramente a la mitosis, incluso con DNA dañado, y fueron incapaces de detener la progresión del ciclo celular, por lo que se dividieron a un menor tamaño. Wee1 se ha descrito en un gran número de eucariontes y se ha determinado que, en la mayoría de ellos, controla la transición G2/M, además numerosos experimentos han demostrado que Wee1 es necesaria para la salida de mitosis y la transición G1/S; sin embargo, no existe una revisión sistemática de la función de Wee1 en cada transición del ciclo celular. En esta revisión se describen los experimentos que establecieron que Wee1 es un regulador clave de la transición G2/M y el papel de Wee1 en la salida de mitosis y en la transición G1/S, donde la actividad de Wee1 evita el inicio desregulado de la replicación y daño en el DNA. Además, se describe en cada punto de regulación, los principales mecanismos que han sido descritos para favorecer la activación o la inactivación de Wee1. Finalmente, se comenta de qué manera se ha aprovechado el papel de Wee1 en las diferentes transiciones del ciclo celular para generar estrategias para el tratamiento del cáncer.


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