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Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates cell cycle progression
1Departments of Surgical Oncology/Molecular and Cellular Oncology and the Breast Cancer Research Program, the University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Abstract:
14-3-3 sigma, implicated in cell cycle arrest by p53, was cloned by expression cloning through cyclin-dependent kinase 2 (CDK2) association. 14-3-3 sigma shares cyclin-CDK2 binding motifs with different cell cycle regulators, including p107, p130, p21(CIP1), p27(KIP1), and p57(KIP2), and is associated with cyclin.CDK complexes in vitro and in vivo. Overexpression of 14-3-3 sigma obstructs cell cycle entry by inhibiting cyclin-CDK activity in many breast cancer cell lines. Overexpression of 14-3-3 sigma can also inhibit cell proliferation and prevent anchorage-independent growth of these cell lines. These findings define 14-3-3 sigma as a negative regulator of the cell cycle progression and suggest that it has an important function in preventing breast tumor cell growth.
Insights
14-3-3 sigma protein, a cell cycle regulator, was identified through its association with cyclin-dependent kinase 2 (CDK2). Its overexpression inhibits cell cycle progression and proliferation, suggesting a role in preventing breast tumor growth.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- 14-3-3 sigma is involved in p53-mediated cell cycle arrest.
- It shares binding motifs with known cell cycle regulators.
Purpose of the Study:
- To clone 14-3-3 sigma using expression cloning.
- To investigate its role in cell cycle regulation and breast cancer.
Main Methods:
- Expression cloning based on cyclin-dependent kinase 2 (CDK2) association.
- In vitro and in vivo association studies with cyclin-CDK complexes.
- Overexpression studies in breast cancer cell lines.
Main Results:
- 14-3-3 sigma was cloned via CDK2 association.
- It associates with cyclin-CDK complexes.
- Overexpression inhibits cyclin-CDK activity, cell cycle entry, proliferation, and anchorage-independent growth in breast cancer cells.
Conclusions:
- 14-3-3 sigma acts as a negative regulator of cell cycle progression.
- It plays a significant role in inhibiting breast tumor cell growth.