Miyatake S, Nakano H, Park S Y, Yamazaki T, Takase K, Matsushime H, Kato A, Saito T
Division of Molecular Genetics, School of Medicine, Chiba University, Japan.
J Exp Med. 1995 Aug 1;182(2):401-8. doi: 10.1084/jem.182.2.401.
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.
通过研究细胞周期调控基因（如G1期细胞周期蛋白及其相关激酶）的功能，在T细胞杂交瘤中研究了激活诱导的生长抑制与细胞周期进程调控之间的关系。抗T细胞受体抗体激活T细胞杂交瘤会诱导细胞周期在G1期停滞，随后导致激活驱动的细胞死亡。激活后细胞周期蛋白D3的信使核糖核酸和蛋白质水平迅速降低，并伴随着生长停滞。尽管残留的细胞周期蛋白D3蛋白与细胞周期蛋白依赖性激酶4蛋白形成复合物，但细胞周期蛋白D3依赖性激酶活性严重受损。经基因工程改造以表达细胞周期蛋白D3的稳定转染子在激活后可克服生长停滞。这些结果表明，通过T细胞受体的激活信号诱导细胞周期蛋白D3表达下调和细胞周期蛋白D3依赖性激酶活性降低，导致T细胞在细胞周期的G1期生长停滞。
