Spitkovsky D, Jansen-Dürr P, Karsenti E, Hoffman I
Angewandte Tumorvirologie, Deutsches Krebsforschungszentrum, Germany.
Oncogene. 1996 Jun 20;12(12):2549-54.
Adenovirus E1A proteins can induce quiescent cells to enter S-phase and also affect the expression of cellular genes including various cell cycle regulators. Here we show that human cdc25A, a tyrosine phosphatase involved in regulation of the G1/S-phase transition of the cell cycle, is a target of the adenovirus E1A protein in virus-infected human fibroblasts. Expression of E1A in quiescent fibroblasts leads to a rapid increase in cdc25A phosphatase activity and also increases both cdc25A and cyclin E gene expression. Inhibition of cdc25A function by antibody injection prevents virus-induced entry into S-phase. These results indicate that induction of high levels of cdc25A and its potential positive regulator cyclin E mediates the ability of E1A to induce S-phase in the presence of antiproliferative signals.
腺病毒E1A蛋白可诱导静止细胞进入S期，还能影响包括多种细胞周期调节因子在内的细胞基因的表达。在此我们表明，人类细胞周期蛋白依赖性激酶25A（cdc25A），一种参与细胞周期G1/S期转换调控的酪氨酸磷酸酶，是病毒感染的人类成纤维细胞中腺病毒E1A蛋白的作用靶点。E1A在静止成纤维细胞中的表达导致cdc25A磷酸酶活性迅速增加，同时也增加了cdc25A和细胞周期蛋白E基因的表达。通过注射抗体抑制cdc25A功能可阻止病毒诱导的细胞进入S期。这些结果表明，在存在抗增殖信号的情况下，高水平的cdc25A及其潜在的正向调节因子细胞周期蛋白E的诱导介导了E1A诱导S期的能力。
