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Spatiotemporal regulation of the anaphase-promoting complex in mitosis
Sushama Sivakumar1, Gary J Gorbsky1
1Cell Cycle and Cancer Biology, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, Oklahoma 73104, USA.
Abstract:
The appropriate timing of events that lead to chromosome segregation during mitosis and cytokinesis is essential to prevent aneuploidy, and defects in these processes can contribute to tumorigenesis. Key mitotic regulators are controlled through ubiquitylation and proteasome-mediated degradation. The APC/C (anaphase-promoting complex; also known as the cyclosome) is an E3 ubiquitin ligase that has a crucial function in the regulation of the mitotic cell cycle, particularly at the onset of anaphase and during mitotic exit. Co-activator proteins, inhibitor proteins, protein kinases and phosphatases interact with the APC/C to temporally and spatially control its activity and thus ensure accurate timing of mitotic events.
Insights
Accurate cell division timing, regulated by the anaphase-promoting complex (APC/C), is vital for preventing aneuploidy and cancer. Its activity is controlled by interacting proteins to ensure proper mitotic events.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Chromosome segregation during mitosis and cytokinesis requires precise timing to prevent aneuploidy.
- Defects in mitotic processes are linked to tumorigenesis.
- Ubiquitylation and proteasome-mediated degradation control key mitotic regulators.
Purpose of the Study:
- To highlight the crucial role of the anaphase-promoting complex (APC/C) in regulating the mitotic cell cycle.
- To explain how APC/C activity is controlled to ensure accurate mitotic timing.
Main Methods:
- Focuses on the regulatory mechanisms of the APC/C.
- Discusses the role of co-activator and inhibitor proteins.
- Mentions the involvement of protein kinases and phosphatases.
Main Results:
- The APC/C is an E3 ubiquitin ligase essential for regulating the mitotic cell cycle.
- APC/C controls key events at the onset of anaphase and during mitotic exit.
- Interactions with co-activators, inhibitors, kinases, and phosphatases modulate APC/C activity.
Conclusions:
- The APC/C is central to the temporal and spatial control of mitosis.
- Proper regulation of APC/C activity is critical for preventing aneuploidy and cancer.
- Understanding APC/C regulation provides insights into cell cycle control and disease.
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