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Subunits and substrates of the anaphase-promoting complex
1Research Institute of Molecular Pathology (IMP), Dr.-Bohr Gasse 7, Vienna, A-1030, Austria. peters@nt.imp.univie.ac.at
Experimental Cell Research
|May 1, 1999
Summary
The anaphase-promoting complex (APC) controls cell cycle progression by targeting key proteins for degradation. This ubiquitination complex is crucial for initiating anaphase and exiting mitosis.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The cell cycle, particularly mitosis, requires precise regulation of protein degradation.
- The anaphase-promoting complex (APC/cyclosome) is a key E3 ubiquitin ligase complex orchestrating these events.
- APC/cyclosome activity is tightly controlled by regulatory factors throughout mitosis and G1.
Purpose of the Study:
- To elucidate the critical roles of the APC/cyclosome in cell cycle progression.
- To detail the substrates targeted by the APC/cyclosome during mitosis.
- To understand the mechanism by which APC/cyclosome-mediated ubiquitination drives key mitotic transitions.
Main Methods:
- Ubiquitination assays to identify APC/cyclosome targets.
- Proteasomal degradation studies using yeast models (budding and fission).
- Biochemical analyses of protein interactions and complex assembly.
Main Results:
- The APC/cyclosome ubiquitinates Pds1 (budding yeast) and Cut2 (fission yeast), enabling sister chromatid separation.
- APC/cyclosome targets cyclin B for degradation, inactivating CDK1 and facilitating mitotic exit.
- The complex mediates the degradation of diverse mitotic regulators, including kinases and replication inhibitors.
Conclusions:
- The APC/cyclosome is indispensable for the metaphase-anaphase transition and mitotic exit.
- APC/cyclosome-dependent proteolysis ensures the timely removal of critical cell cycle regulators.
- Dysregulation of APC/cyclosome function can lead to cell cycle arrest or aberrant proliferation.