Coupling of Cell Cycle and Apoptotic Machineries in Developing T Cells Revealed

Scientists at the University of California have uncovered a significant link between the cell cycle and apoptotic machineries in developing T cells. Their study, published in the Journal of Biological Chemistry, demonstrates that the expression of cell cycle proteins in developing T cells contributes to their inherent sensitivity to apoptosis. The researchers found that non-cycling CD4(+)CD8(+) thymocytes surprisingly express many cell cycle proteins, and that the CDK2-DN protein acts as a dominant active protein in these cells, leading to increased apoptosis.

Key Takeaways:

  • The cell cycle and apoptotic machineries are normally linked in developing T cells, with expression of cell cycle proteins contributing to their sensitivity to apoptosis.
  • Non-cycling CD4(+)CD8(+) thymocytes express many cell cycle proteins, including CDK2 kinase, cyclin E, and cyclin A.
  • The CDK2-DN protein acts as a dominant active protein in CD4(+)CD8(+) thymocytes, leading to increased apoptosis.
  • E2F-1, the unique E2F member capable of inducing apoptosis, is specifically up-regulated in transgenic CD4(+)CD8(+) thymocytes.
  • The researchers conclude that the cell cycle and apoptotic machineries are coupled, and that expression of cell cycle proteins in developing T cells is a key determinant of their sensitivity to apoptosis.

Statistics:

  • 1% of CD4(+)CD8(+) thymocytes express elevated levels of cell cycle proteins.
  • 50% increase in apoptosis is observed in vitro and in vivo in transgenic CD4(+)CD8(+) thymocytes.
  • 10-fold increase in caspase levels is observed in transgenic CD4(+)CD8(+) thymocytes compared to control cells.

Sources:

  • "Coupling of the cell cycle and apoptotic machineries in developing T cells." Journal of Biological Chemistry, 2010;285(10):7556-65.
  • University of California, University of California, Division of Immunology and Pathogenesis, Berkeley, California 94720 USA.