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.
Induction of G1 arrest by down-regulation of cyclin D3 in T cell hybridomas.
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S Miyatake, H Nakano, S Y Park, T Yamazaki, K Takase, H Matsushime, A Kato, T Saito; Induction of G1 arrest by down-regulation of cyclin D3 in T cell hybridomas.. J Exp Med 1 August 1995; 182 (2): 401–408. doi: https://doi.org/10.1084/jem.182.2.401
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