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Studying Proteolysis of Cyclin B at the Single Cell Level in Whole Cell Populations
Published on: September 17, 2012
Cyclin E overexpression impairs progression through mitosis by inhibiting APC(Cdh1)
Jamie M Keck1, Matthew K Summers, Donato Tedesco
1Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037.
The Journal of Cell Biology
|August 1, 2007
Summary
Overexpression of cyclin E causes errors in chromosome alignment during cell division, leading to polyploidy and potentially contributing to cancer development. This occurs by inhibiting the anaphase-promoting complex (APC/Cdh1).
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Overexpression of cyclin E, a cyclin-dependent kinase 2 activator, is implicated in human cancers.
- Previous studies in cell culture suggest cyclin E overexpression induces aneuploidy and polyploidy, hinting at a role in tumorigenesis.
Purpose of the Study:
- To investigate the direct impact of cyclin E overexpression on mitotic progression.
- To elucidate the molecular mechanisms by which cyclin E overexpression leads to chromosomal abnormalities.
Main Methods:
- Utilized cell culture models to study the effects of forced cyclin E expression.
- Analyzed mitotic progression, chromosome alignment, and cell division outcomes.
- Investigated the interaction between cyclin E and the anaphase-promoting complex (APC/Cdh1).
Main Results:
- Cyclin E overexpression directly disrupts late mitotic prometaphase progression before chromosome alignment.
- Observed phenotypes include failure of chromosome segregation (polyploidy) and progression to anaphase with misaligned chromosomes.
- Demonstrated that overexpressed cyclin E inhibits anaphase-promoting complex (APC/Cdh1) activity, causing accumulation of APC/Cdh1 substrates like securin and cyclin B1.
Conclusions:
- Cyclin E overexpression directly causes mitotic errors, including polyploidy, by inhibiting APC/Cdh1.
- The accumulation of securin and cyclin B1 mediates the observed cyclin E-driven mitotic defects.
- These findings provide a mechanistic link between cyclin E overexpression, mitotic dysfunction, and potential tumorigenesis.
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