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Updated: Jun 13, 2026
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Live Cell Imaging to Assess the Dynamics of Metaphase Timing and Cell Fate Following Mitotic Spindle Perturbations
Published on: September 20, 2019
Substrate degradation by the anaphase promoting complex occurs during mitotic slippage
Jinho Lee1, Jin Ah Kim, Robert L Margolis
1Sidney Kimmel Cancer Center, San Diego, CA, USA.
Cell Cycle (Georgetown, Tex.)
|May 4, 2010
Summary
Cancer drugs activate cell cycle checkpoints, but cells can still divide. This study shows the anaphase-promoting complex (APC) activates during cell division slippage, enabling cells to exit mitosis despite checkpoint activation.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Microtubule targeting drugs are chemotherapy agents that activate the spindle assembly checkpoint (SAC).
- The SAC prevents premature anaphase by inhibiting the anaphase-promoting complex (APC).
- Cells can exit mitosis via slippage when the SAC is continuously activated.
Purpose of the Study:
- To investigate whether the anaphase-promoting complex (APC) is activated during mitotic slippage.
- To determine if APC activation occurs despite sustained spindle assembly checkpoint (SAC) activation.
Main Methods:
- Utilized nocodazole to block cells in mitosis.
- Assessed degradation of APC substrates during mitotic slippage.
- Performed knockdown of Cdc20 and Cdh1, APC activators, to confirm APC activation.
Main Results:
- Mitotic APC substrates were degraded upon mitotic slippage.
- Knockdown of Cdc20 and Cdh1 prevented APC substrate degradation during slippage.
- Demonstrated APC activation during mitotic slippage into interphase.
Conclusions:
- The anaphase-promoting complex (APC) is activated during mitotic slippage, even with sustained spindle assembly checkpoint (SAC) activation.
- Chemotherapy's SAC activation may not indefinitely prevent APC activation, impacting cell cycle progression.
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