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Structural interconversions of the anaphase-promoting complex/cyclosome (APC/C) regulate cell cycle transitions
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, United Kingdom.
Current Opinion in Structural Biology
|December 22, 2019
Summary
The anaphase-promoting complex/cyclosome (APC/C) regulates cell cycle transitions by degrading key proteins. Its structural changes, driven by competing motifs, control its function and substrate specificity.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The anaphase-promoting complex/cyclosome (APC/C) is a crucial E3 ubiquitin ligase regulating cell cycle progression.
- APC/C controls cell cycle transitions through ubiquitin-dependent degradation of specific regulators.
- Understanding APC/C's regulation is vital for comprehending cell cycle control.
Purpose of the Study:
- To review structural and mechanistic insights into APC/C function.
- To explain how APC/C modifications govern its interconversion between functional states.
- To elucidate the role of short linear motifs (SLIMs) in APC/C regulation.
Main Methods:
- Review of structural and mechanistic studies.
- Analysis of functional studies on APC/C.
- Integration of data to explain APC/C molecular mechanisms.
Main Results:
- APC/C activity and substrate selection are tightly regulated.
- Modifications of the core APC/C drive its structural and functional state changes.
- Competition among SLIMs for APC/C binding sites is a unifying regulatory mechanism.
Conclusions:
- Structural interconversions are key to APC/C's control over cell cycle phase transitions.
- SLIMs play a critical role in mediating APC/C substrate specificity and coactivator/inhibitor interactions.
- A comprehensive understanding of APC/C mechanisms relies on integrating structural, mechanistic, and functional data.
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