Molecular mechanism of cell cycle regulation in human T cells

细胞周期和细胞生长的分子机制主要以成纤维细胞为研究对象。除部分穴位外，适用于淋巴细胞；例如，细胞周期转录因子E2F1的过度表达在大鼠成纤维细胞中诱导细胞周期进展，但在人T细胞中却没有。我们研究了il -2诱导人T细胞细胞周期进程的分子机制。IL-2诱导E2F4活化，在静息期通过与Rb家族成员p130形成复合物而失活。一旦用IL-2处理，T细胞就会降低细胞周期蛋白依赖性激酶（CDKs）、p19和p27的水平，并增加CDKs和d型细胞周期蛋白基因的表达，从而诱导CDK活性。活化的CDKs使pRb家族成员p130、p107和pRb磷酸化，导致E2F4活性形式从p130复合物中释放出来。事实上，我们观察到，当T细胞受到IL-2刺激时，由E2F4和p130组成的复合体（被认为是静止型复合体）的数量减少，而自由E2F4分子的数量增加，这表明了结合DNA元素的能力。此外，IL-2将E2F复合物转变为含有E2F4、p130、p107、CDK2和周期蛋白a的S期1，IL-2诱导连锁反应激活E2F，通过触发CDKs的激活来引导细胞周期进程和细胞生长。

Molecular mechanism of the cell cycle and cell growth has been studied mainly with fibroblastic cells. The mechanism is applicable to lymphocytes except for some points ; for example overexpression of a cell cycle transcription factor E2F1 induces cell cycle progression in rat fibroblasts but not in human T cells. We studied the molecular mechanism of IL-2-induced cell cycle progression in human T cells. IL-2 induced activation of E2F4, which was inactivated in resting phase by the fomation of complex with p130, a member of the Rb family. Once treated with IL-2, T cells reduced levels of cyclin-dependent kinase (CDKs), p19 and p27, and increased expression of genes for CDKs and D-type cyclins, resulting in induction of CDK activities. Activated CDKs phosphorylated the pRb family members, p130, p107 and pRb, which led release of active form of E2F4 from the complex with p130. Indeed, we observed, when T cells were stimulated with IL-2, a decrease in amount of the complex consisting of E2F4 and p130, which is thought to be a resting type complex, and an increase in amount of free E2F4 molecules, which showed the ablity to bind DNA elements. In addition, IL-2 brought transition of the E2F complex to S phase one containing E2F4, p130, p107, CDK2 and cyclin A. Collectively, IL-2 induces a chain reaction to activate E2F that leads cell cycle progression and cell growth by triggering activation of CDKs.