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Induction of G1 arrest by down-regulation of cyclin D3 in T cell hybridomas
S Miyatake1, H Nakano, S Y Park
1Division of Molecular Genetics, School of Medicine, Chiba University, Japan.
Abstract:
The relationship between activation-induced growth inhibition and regulation of the cell cycle progression was investigated in T cell hybridomas by studying the function of the cell cycle-regulating genes such as G1 cyclins and their associated kinases. Activation of T cell hybridomas by anti-T cell receptor antibody induces growth arrest at G1 phase of the cell cycle and subsequently results in activation-driven cell death. Rapid reduction of both messenger RNA and protein level of the cyclin D3 is accompanied by growth arrest upon activation. Although the residual cyclin D3 protein forms a complex with cdk4 protein, cyclin D3-dependent kinase activity is severely impaired. Stable transfectants engineered to express cyclin D3 override the growth arrest upon activation. These results imply that the activation signal through T cell receptor induces the down-regulation of cyclin D3 expression and cyclin D3-dependent kinase activity, leading to growth arrest in G1 phase of the cell cycle in T cells.
Insights
T cell activation by anti-T cell receptor antibody causes growth arrest in G1 phase. This is linked to reduced cyclin D3 expression and impaired kinase activity, preventing T cell proliferation.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- T cell activation is crucial for immune responses.
- Cell cycle regulation governs T cell proliferation and survival.
- Understanding T cell growth inhibition mechanisms is vital.
Purpose of the Study:
- To investigate the link between T cell activation-induced growth inhibition and cell cycle regulation.
- To elucidate the role of G1 cyclins and kinases in T cell cycle arrest.
Main Methods:
- Studied T cell hybridomas activated by anti-T cell receptor antibody.
- Analyzed messenger RNA and protein levels of cyclin D3.
- Assessed cyclin D3-dependent kinase activity.
- Utilized stable transfectants engineered for cyclin D3 expression.
Main Results:
- T cell activation induced G1 phase growth arrest and subsequent cell death.
- Cyclin D3 mRNA and protein levels rapidly decreased upon activation.
- Cyclin D3-cdk4 complex formation occurred, but kinase activity was impaired.
- Overexpression of cyclin D3 in transfectants prevented activation-induced growth arrest.
Conclusions:
- T cell receptor signaling down-regulates cyclin D3 expression and activity.
- This down-regulation leads to G1 phase cell cycle arrest in T cells.
- Cyclin D3 plays a critical role in preventing T cell proliferation upon activation.