Ishii T, Shimizu M, Kanayama Y, Nakada S, Nojima H, Oda K
Department of Biological Science and Technology, Science University of Tokyo, Chiba, Japan.
Exp Cell Res. 1993 Oct;208(2):407-14. doi: 10.1006/excr.1993.1262.
The differential activation of cyclin and cyclin-dependent kinase genes by the adenovirus E1A gene product (E1A) or serum factors was studied with a rat 3Y1 derivative cell line, g12-21, in which the E1A12S cDNA can be expressed in response to dexamethasone (dex). The induction of DNA synthesis in quiescent g12-21 cells occurred within 12 h after serum stimulation, while it occurred within 8 h after treatment with dex. The expression of cyclin D1 and E genes in the serum-stimulated cells was induced in mid G1 and mid to late G1, respectively, while that of the cyclin D1 gene was not induced and the induction of the cyclin E gene was shifted to the G1/S boundary in the dex-treated cells. The cdk2 gene was induced in late G1 and cdc2 and cyclin A genes at the G1/S boundary in both serum-stimulated and dex-treated cells. These results suggest that E1A skips cell cycle events which normally occur in early to mid G1 and may directly activate late-response genes. Analysis of the transcription factor E2F complexes formed in the promoter regions of cdc2 and dihydrofolate reductase genes showed that the amount of complexes formed is maximal at the G1/S boundary, but decreases in S phase when these genes are transcribed extensively.
利用大鼠3Y1衍生细胞系g12 - 21研究了腺病毒E1A基因产物（E1A）或血清因子对细胞周期蛋白和细胞周期蛋白依赖性激酶基因的差异激活作用，在该细胞系中，E1A12S cDNA可响应地塞米松（dex）表达。静止的g12 - 21细胞在血清刺激后12小时内发生DNA合成诱导，而在用dex处理后8小时内发生。血清刺激细胞中细胞周期蛋白D1和E基因的表达分别在G1期中期和G1期中期至后期被诱导，而在dex处理的细胞中细胞周期蛋白D1基因未被诱导，细胞周期蛋白E基因的诱导转移至G1/S边界。在血清刺激和dex处理的细胞中，cdk2基因在G1期后期被诱导，cdc2和细胞周期蛋白A基因在G1/S边界被诱导。这些结果表明，E1A跳过了通常在G1期早期至中期发生的细胞周期事件，可能直接激活晚期反应基因。对在cdc2和二氢叶酸还原酶基因启动子区域形成的转录因子E2F复合物的分析表明，形成的复合物数量在G1/S边界处最大，但在这些基因大量转录的S期减少。
