The mitotic checkpoint complex (MCC): looking back and forth after 15 years
1Department of Biological Sciences, University of Toledo, 2801 West Bancroft St., Toledo, OH 43606, USA.
Abstract:
The mitotic checkpoint is a specialized signal transduction pathway that contributes to the fidelity of chromosome segregation. The signaling of the checkpoint originates from defective kinetochore-microtubule interactions and leads to formation of the mitotic checkpoint complex (MCC), a highly potent inhibitor of the Anaphase Promoting Complex/Cyclosome (APC/C)-the E3 ubiquitin ligase essential for anaphase onset. Many important questions concerning the MCC and its interaction with APC/C have been intensively investigated and debated in the past 15 years, such as the exact composition of the MCC, how it is assembled during a cell cycle, how it inhibits APC/C, and how the MCC is disassembled to allow APC/C activation. These efforts have culminated in recently reported structure models for human MCC:APC/C supra-complexes at near-atomic resolution that shed light on multiple aspects of the mitotic checkpoint mechanisms. However, confusing statements regarding the MCC are still scattered in the literature, making it difficult for students and scientists alike to obtain a clear picture of MCC composition, structure, function and dynamics. This review will comb through some of the most popular concepts or misconceptions about the MCC, discuss our current understandings, present a synthesized model on regulation of CDC20 ubiquitination, and suggest a few future endeavors and cautions for next phase of MCC research.
Insights
The mitotic checkpoint complex (MCC) ensures accurate chromosome segregation by inhibiting the Anaphase Promoting Complex/Cyclosome (APC/C). Recent structural models clarify MCC:APC/C interactions, resolving long-standing questions about MCC function and regulation.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The mitotic checkpoint is crucial for accurate chromosome segregation during cell division.
- It functions by forming the mitotic checkpoint complex (MCC), which inhibits the Anaphase Promoting Complex/Cyclosome (APC/C).
- Despite extensive research, ambiguities persist regarding MCC composition, assembly, inhibition, and disassembly mechanisms.
Purpose of the Study:
- To clarify misconceptions surrounding the mitotic checkpoint complex (MCC).
- To synthesize current understanding of MCC structure, function, and dynamics.
- To present a refined model for MCC regulation of CDC20 ubiquitination.
Main Methods:
- Literature review and synthesis of existing research.
- Analysis of recently published structural models of MCC:APC/C supra-complexes.
- Critical evaluation of debated concepts and misconceptions in the field.
Main Results:
- Recent high-resolution structural data provide insights into MCC:APC/C interactions.
- A clearer picture of MCC composition, assembly, and inhibitory mechanisms is emerging.
- Synthesized model addresses regulation of CDC20 ubiquitination by the MCC.
Conclusions:
- Recent structural studies have significantly advanced our understanding of the mitotic checkpoint.
- Addressing remaining misconceptions is vital for clear comprehension of MCC function.
- Future research should focus on refining MCC dynamics and regulation, with careful consideration of existing data.
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