CCDC68 Maintains Mitotic Checkpoint Activation by Promoting CDC20 Integration into the MCC
Qi Li1, Qingzhou Chen1, Tao Zheng1
1Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, College of Life Sciences, Peking University, Beijing, 100871, China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|July 17, 2024
Summary
CCDC68 is a newly identified outer kinetochore protein that stabilizes the mitotic checkpoint complex (MCC) by interacting with CDC20. This interaction ensures robust spindle assembly checkpoint (SAC) activation, maintaining chromosomal stability during cell division.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- The spindle assembly checkpoint (SAC) is crucial for accurate chromosome segregation.
- The mitotic checkpoint complex (MCC) inhibits the anaphase-promoting complex/cyclosome (APC/C) to prevent premature mitotic exit.
- The precise mechanisms of MCC assembly at unattached kinetochores remain incompletely understood.
Purpose of the Study:
- To investigate the role of CCDC68 in the spindle assembly checkpoint.
- To elucidate how unattached kinetochores mediate MCC formation and checkpoint activation.
Main Methods:
- Immunofluorescence microscopy to determine CCDC68 localization.
- Co-immunoprecipitation assays to identify protein interactions.
- Ubiquitination assays to assess protein stability.
Main Results:
- CCDC68 localizes to outer kinetochores, particularly at unattached ones.
- CCDC68 interacts with CDC20, inhibiting its autoubiquitination and MCC disassembly.
- CCDC68 restrains APC/C activation, ensuring prolonged SAC signaling.
Conclusions:
- CCDC68 is essential for stabilizing the MCC via CDC20.
- CCDC68 plays a critical role in maintaining SAC activation for chromosomal stability.
- The findings reveal CCDC68 as a key regulator of mitotic checkpoint fidelity.
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