Single amino acid (arginine) deprivation induces G1 arrest associated with inhibition of Cdk4 expression in cultured human diploid fibroblasts
Single amino acid (arginine) deprivation induces G1 arrest associated with inhibition of Cdk4 expression in cultured human diploid fibroblasts
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DOI：
10.1006/excr.1999.4779
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发表时间：
2000-03-15
影响因子：
3.7
通讯作者：
Wheatley, DN
中科院分区：
文献类型：
--
作者：
Lamb, J;Wheatley, DN
从自由循环的早期代人成纤维细胞中提取一种氨基酸（精氨酸）导致细胞增殖停止，其特征是细胞周期G1期的细胞积累。这种抑制伴随着细胞周期蛋白D1和细胞周期蛋白e相关激酶活性的抑制以及低磷酸化视网膜母细胞瘤蛋白的出现。缺乏精氨酸的细胞存活时间超过4天，并且可以通过氨基酸的恢复同步重新进入细胞周期，具有从静止状态退出的动力学特征。当从培养基中省略精氨酸时，血清停药对细胞的刺激不会导致s期进入。虽然细胞周期蛋白DI在正常时间内积累，但cdk4在氨基酸充满的培养基中再刺激后增加，当精氨酸缺失时不被诱导。这些结果表明，精氨酸剥夺——与其他“次优”条件一样——抑制了正常人类细胞通过限制点的通道，并暗示cdk4是氨基酸敏感细胞周期控制的关键调控元件。(C) 2000年学术出版社。
Withdrawal of a single amino acid (arginine) from freely cycling early passage primary human fibroblasts caused a halt to proliferation, characterized by an accumulation of cells in the G1 phase of the cell cycle. This arrest was accompanied by the suppression of cyclin D1- and cyclin E-associated kinase activities and the appearance of hypophosphorylated retinoblastoma protein. Arginine-deprived cells remained viable for in excess of 4 days and could be made to synchronously reenter the cell cycle by restoration of the amino acid, with kinetics characteristic of exit from a quiescent state. Stimulation of cells arrested by serum withdrawal did not result in S-phase entry when arginine was omitted from the culture medium. Although cyclin DI accumulated on normal schedule, cdk4, which increased following restimulation in amino acid-replete medium, was not induced when arginine was absent. These results suggest that arginine deprivation-in common with other "suboptimal" conditions-inhibits the passage of normal human cells through the restriction point and implicate cdk4 as the key regulatory element in amino acid-sensitive cell cycle control. (C) 2000 Academic Press.