Dual inhibition of Cdc20 by the spindle checkpoint |
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Authors: | Rey-Huei Chen |
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Institution: | (1) Institute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan |
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Abstract: | The metaphase-to-anaphase transition is triggered by the Anaphase-Promoting Complex (APC), an E3 ubiquitin ligase that targets
proteins for degradation, leading to sister chromatid separation and mitotic exit. The function of APC is controlled by the
spindle checkpoint that delays anaphase onset in the presence of any chromosome that has not established bipolar attachment
to the mitotic spindle. In this way, the checkpoint ensures accurate chromosome segregation. The spindle checkpoint is mostly
activated from kinetochores that are not attached to microtubules or not under tension that is normally generated from bipolar
attachment. These kinetochores recruit several spindle checkpoint proteins to assemble an inhibitory complex composed of checkpoint
proteins Mad2, Bub3, and Mad3/BubR1. This complex binds and inhibits Cdc20, an activator and substrate adaptor for APC. In
addition, the checkpoint complex promotes Cdc20 degradation, thus lowering Cdc20 protein level upon checkpoint activation.
This dual inhibition on Cdc20 likely ensures that the spindle checkpoint is sustained even when the cell contains only a single
unattached kinetochore. |
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Keywords: | spindle checkpoint kinetochore Cdc20 anaphase-promoting complex |
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