Related Experiment Video
Updated: Jul 29, 2026
10:54
Studying Proteolysis of Cyclin B at the Single Cell Level in Whole Cell Populations
Published on: September 17, 2012
Tumor-specific proteolytic processing of cyclin E generates hyperactive lower-molecular-weight forms
1Division of Molecular Medicine, Wadsworth Center, Albany, New York 12201-0509, USA.
Molecular and Cellular Biology
|August 18, 2001
Summary
Lower-molecular-weight cyclin E (LMW CE) isoforms are hyperactive and drive cancer cell proliferation. Proteolytic cleavage generates these oncogenic forms, impacting cell cycle progression and patient outcomes in breast cancer.
Area of Science:
- Cell Biology
- Molecular Oncology
- Biochemistry
Background:
- Cyclin E is a G(1) cyclin crucial for cell cycle progression into S-phase.
- Overexpressed and lower-molecular-weight (LMW) cyclin E isoforms are observed in breast cancer, correlating with poor patient outcomes.
Purpose of the Study:
- To investigate the biochemical activity and biological function of LMW cyclin E isoforms found in breast tumors.
- To identify the mechanisms responsible for generating LMW cyclin E isoforms.
Main Methods:
- Biochemical assays and mutational analysis to study cyclin E proteolysis.
- Transfection of normal cells with LMW cyclin E to assess functional impact.
- In vitro cleavage assays using elastase class serine proteases.
Main Results:
- LMW cyclin E isoforms exhibit higher biochemical activity, phosphorylating substrates like histone H1 and GST-Rb.
- Overexpression of nuclear-localized LMW cyclin E enhances G(1)-to-S and G(2)/M phase entry in normal cells.
- Elastase class serine proteases selectively cleave cyclin E in vitro, generating LMW forms similar to those in tumors.
Conclusions:
- Proteolytic processing of cyclin E generates hyperactive LMW isoforms, contributing to aberrant cell cycle progression in cancer.
- These modified LMW cyclin E isoforms play a role in the defective S-phase entry and exit observed in tumor cells.
Related Concept Videos
01:45Positive Regulator Molecules
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
02:39Positive Regulator Molecules
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
02:34Inhibition of Cdk Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
02:38Mitogens and the Cell Cycle
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
00:50Anaphase Promoting Complex
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...