Coupling of the cell cycle and apoptotic machineries in developing T cells
Ling Xue1, Yuefang Sun, Leslie Chiang
1Cancer Research Laboratory and Department of Molecular and Cell Biology, Division of Immunology and Pathogenesis, University of California, Berkeley, California 94720, USA.
The Journal of Biological Chemistry
|January 14, 2010
Summary
Cell cycle proteins unexpectedly promote apoptosis in developing T cells. This study reveals a direct link between cell cycle machinery and programmed cell death in thymocytes, impacting T cell development.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Proliferation and apoptosis are opposing cellular processes.
- The molecular basis for thymocyte sensitivity to apoptosis is unclear.
- Noncycling thymocytes express cell cycle proteins.
Purpose of the Study:
- Investigate the role of cell cycle proteins in CD4(+)CD8(+) thymocyte apoptosis.
- Determine the molecular mechanisms linking cell cycle and apoptosis in T cell development.
Main Methods:
- Generated transgenic mice expressing a dominant-negative CDK2 mutant (CDK2-DN).
- Analyzed T cell populations for cell cycle protein and caspase expression.
- Assessed apoptosis in vitro and in vivo.
Main Results:
- CDK2-DN acted as a dominant active protein in CD4(+)CD8(+) thymocytes, increasing cell cycle activity.
- Elevated CDK2 kinase activity, cyclin E, and cyclin A levels were observed.
- Apoptosis was significantly enhanced, with specific upregulation of E2F-1 in transgenic thymocytes.
Conclusions:
- The cell cycle and apoptotic machineries are intrinsically linked.
- Expression of cell cycle proteins in developing T cells contributes to their sensitivity to apoptosis.
- This linkage is crucial for normal T cell development.
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