Molecular mechanism of cell cycle regulation in human T cells

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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.