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El punto de control de abscisión mediado por Aurora B protege contra la tetraploidización
Patrick Steigemann1, Claudia Wurzenberger, Michael H A Schmitz
1Institute of Biochemistry, Swiss Institute of Technology Zurich, ETHZ, Zurich, Switzerland.
Cell
|February 11, 2009
Resumen
Un nuevo mecanismo de control de la división celular previene la tetraploidización que promueve el cáncer en las células humanas. La actividad de la cinasa Aurora B, regulada por la segregación cromosómica, asegura la división celular adecuada y suprime el crecimiento celular anormal.
Área de la Ciencia:
- Biología celular Biología celular.
- Genética La genética.
- Investigación del cáncer Investigación del cáncer.
Sus antecedentes:
- Las anomalías genómicas, incluida la tetraploidización, son características del cáncer y surgen de una citocinesis fallida.
- La tetraploidización se considera un evento temprano en el desarrollo del cáncer, destacando la necesidad de comprender sus mecanismos de prevención.
Objetivo del estudio:
- Para dilucidar un mecanismo de control de la división celular que impide la tetraploidización en las células humanas con errores en la segregación cromosómica.
- Para investigar el papel de la Aurora B quinasa en la regulación de la citoquinesis y la prevención de la tetraploidización.
Principales métodos:
- Análisis de células humanas con segregación cromosómica perturbada.
- Investigando la actividad de la Aurora B quinasa durante la división celular.
- Estudiando la fosforilación de la proteína mitótica parecida a la quinesina 1 (Mklp1).
Principales resultados:
- Se encontró que la inactivación de Aurora B promueve la finalización de la citocinesis por abscisión.
- Los puentes cromosómicos mantuvieron la actividad de Aurora B, retrasando la abscisión y previniendo la tetraploidización a través de la regresión de surcos.
- Se identificó una vía que involucra la fosforilación de Aurora B y Mklp1 como crucial para suprimir la tetraploidización.
Conclusiones:
- Aurora B actúa como un sensor de la cromatina no segregada en el sitio de la escisión durante la división celular.
- La abscisión celular está estrechamente coordinada con la finalización de la segregación cromosómica en las células humanas para evitar la tetraploidización.
- Este mecanismo protege contra la formación de cáncer al mantener la estabilidad genómica.
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