Cdk1-phosphorylated CUEDC2 promotes spindle checkpoint inactivation and chromosomal instability
Yan-Fei Gao1, Teng Li, Yan Chang
1Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing 100850, China.
Nature Cell Biology
|July 12, 2011
Summary
CUEDC2 is a cell-cycle regulator that promotes the inactivation of the spindle assembly checkpoint (SAC) and activates the anaphase-promoting complex/cyclosome (APC/C). CUEDC2 dysregulation contributes to cancer by causing chromosomal instability.
Area of Science:
- Cell Biology
- Cancer Biology
- Molecular Oncology
Background:
- Aneuploidy and chromosomal instability are hallmarks of human cancers.
- Defects in the spindle assembly checkpoint (SAC) can lead to these abnormalities by impairing accurate chromosome segregation.
- The SAC regulates the anaphase-promoting complex/cyclosome (APC/C) to ensure proper cell division.
Purpose of the Study:
- To investigate the role of CUEDC2 in cell-cycle regulation and its potential contribution to cancer.
- To elucidate the mechanism by which CUEDC2 influences SAC activity and APC/C regulation.
Main Methods:
- Depletion and overexpression of CUEDC2 in cell models.
- Analysis of cell-cycle progression and checkpoint control.
- Investigation of protein-protein interactions involving CUEDC2, Cdc20, and Mad2 during mitosis.
Main Results:
- CUEDC2 acts as a cell-cycle regulator, promoting SAC inactivation and APC/C activation.
- CUEDC2 is phosphorylated by Cdk1 during mitosis, facilitating its interaction with Cdc20.
- Depletion of CUEDC2 delays cell division, while its overexpression leads to chromosome missegregation and aneuploidy.
- CUEDC2 is frequently overexpressed in various human tumors.
Conclusions:
- CUEDC2 is a critical regulator of mitosis progression by controlling SAC/APC/C activity.
- CUEDC2 dysregulation and subsequent chromosomal instability may drive tumor development.
- Targeting CUEDC2 could offer a novel therapeutic strategy for cancers characterized by aneuploidy.
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