Aurora-A Overexpression Leads to Override of the Microtubule-Kinetochore Attachment Checkpoint

Mad2 binding to kinetochores during metaphase-anaphase transition in HeLa cells. A. (Top)

In prophase every kinetochore is decorated with Mad2. Once a kinetochore is captured by microtubules, Mad2 labelling disappears. Metaphase-to-anaphase transition will be triggered only when all kinetochores are captured. However, any kinetochore remaining decorated with Mad2 (i.e., unattached chromosome) will activate the mitotic checkpoint leading to cell cycle arrest (Middle). In the presence of overexpressed aurora-A, the cell ignores the Mad2 signal and triggers metaphase exit (Bottom). B. Mad2 is an inhibitor of Cdc20, a known APC/C activator. Overexpression of aurora-A interferes with the Mad2–Cdc20 signal that promotes progression to anaphase (14).