Molecular mechanism of cell cycle progression induced by the oncogene product Tax of human T-cell leukemia virus type I
Molecular mechanism of cell cycle progression induced by the oncogene product Tax of human T-cell leukemia virus type I
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DOI：
10.1038/sj.onc.1204304
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发表时间：
2001-04-19
期刊：
影响因子：
8
通讯作者：
Nakamura, M
中科院分区：
文献类型：
--
作者：
Iwanaga, R;Ohtani, K;Nakamura, M
人T细胞白血病病毒I型（HTLV-I）的反式激活蛋白Tax至少部分地通过其刺激细胞生长的能力在成人T细胞白血病的发展中起重要作用。我们以前报道过Tax诱导人T细胞系Kit 225细胞从G 0/G1期进入S期和G2/M期。为了阐明Tax诱导细胞周期进程的分子机制，我们系统地研究了Tax对与细胞周期进程相关的生化事件的影响，将Tax引入静息的Kit 225细胞中诱导G1/S转换调节级联的激活，包括细胞周期蛋白依赖性激酶2（CDK 2）和CDK 4的激活，Rb家族蛋白的磷酸化和游离E2 F的增加，Tax对NF-κ B的激活主要是由于Tax诱导细胞周期调控分子cyclin D2、cyclin E、E2 F1、CDK 2、CDK 4和CDK 6的基因表达，以及Tax诱导CDK抑制剂p19（INK 4d）和p27（Kip 1）的减少。这些结果表明Tax介导的细胞周期调控分子基因的反式激活在Tax诱导的细胞周期进程中的重要作用。
The trans-activator protein Tax of human T-cell leukemia virus type I(HTLV-I) plays an important role in the development of adult T-cell leukemia through, at least in part, its ability to stimulate cell growth. We previously reported that Tax induced cell cycle progression from G0/G1 phase to S and G2/M phases in human T-cell line Kit 225 cells. To elucidate molecular mechanism of Tax-induced cell cycle progression, we systematically examined the effects of Tax on biochemical events associated with cell cycle progression, Introduction of Tax into resting Kit 225 cells induced activation of the G1/S transition regulation cascade consisting of activation of cyclin dependent kinase 2 (CDK2) and CDK4, phosphorylation of the Rb family proteins and an increase in free E2F, The kinase activation was found to result from Tax-induced expression of genes for cell cycle regulatory molecules including cyclin D2, cyclin E, E2F1, CDK2, CDK4 and CDK6, and Tax-induced reduction of CDK inhibitors p19(INK4d) and p27(Kip1), These modulations by Tax always paralleled the ability of Tax to activate the NF-kappaB transcription pathway. These results indicate the important role of Tax-mediated trans-activation of the genes for cell cycle regulatory molecules in Tax-induced cell cycle progression.