Clark W, Gillespie D A
Beatson Institute for Cancer Research, Cancer Research Campaign Beatson Laboratories, Bearsden, Glasgow, United Kingdom.
Cell Growth Differ. 1997 Apr;8(4):371-80.
To gain insight into the mechanism of action of the v-Jun oncoprotein, we compared the growth and cell cycle behavior of normal and v-Jun-transformed fibroblasts. We show that v-Jun induces marked alterations in cell cycle regulation in both the presence and absence of serum growth factors. During asynchronous growth, v-Jun-transformed fibroblasts divide more rapidly than their normal counterparts, owing to a reduction in the length of the G1 phase of the cell cycle. When deprived of serum mitogens, normal fibroblasts exit the cycle and enter a reversible state of quiescence (G0). In contrast, v-Jun-transformed fibroblasts continue to cycle and maintain increased levels of retinoblastoma tumor suppressor protein phosphorylation and elevated expression of cell cycle-dependent markers such as cyclin A, cyclin-dependent protein kinase 2 (CDK2), and CDC2. v-Jun-transformed fibroblasts nevertheless remain wholly dependent on growth factors for cell multiplication, because cell cycle progression in the absence of serum is accompanied by high rates of apoptotic cell death. We conclude that v-Jun shares the capacity of the Myc, E1A, and E2F oncoproteins to promote both cell cycle progression and apoptosis under conditions of mitogen depletion.
为深入了解v-Jun癌蛋白的作用机制，我们比较了正常成纤维细胞和v-Jun转化的成纤维细胞的生长及细胞周期行为。我们发现，无论有无血清生长因子，v-Jun都会诱导细胞周期调控发生显著改变。在异步生长过程中，v-Jun转化的成纤维细胞比正常成纤维细胞分裂更快，这是由于细胞周期G1期长度缩短所致。当缺乏血清促有丝分裂原时，正常成纤维细胞退出细胞周期并进入可逆的静止状态（G0期）。相比之下，v-Jun转化的成纤维细胞继续循环，并维持视网膜母细胞瘤肿瘤抑制蛋白磷酸化水平的升高以及细胞周期依赖性标志物如细胞周期蛋白A、细胞周期蛋白依赖性蛋白激酶2（CDK2）和细胞分裂周期蛋白2（CDC2）的高表达。然而，v-Jun转化的成纤维细胞的细胞增殖仍然完全依赖生长因子，因为在无血清条件下细胞周期进程伴随着高比率的凋亡性细胞死亡。我们得出结论，在有丝分裂原缺乏的条件下，v-Jun与Myc、E1A和E2F癌蛋白一样，具有促进细胞周期进程和凋亡的能力。
