Cell cycle re-entry following chemically-induced cell cycle synchronization leads to elevated p53 and p21 protein levels
Cell cycle re-entry following chemically-induced cell cycle synchronization leads to elevated p53 and p21 protein levels
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DOI：
10.1038/sj.onc.1201441
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发表时间：
1997-11-27
期刊：
影响因子：
8
通讯作者：
Pietenpol, JA
中科院分区：
文献类型：
--
作者：
Ji, C;Marnett, LJ;Pietenpol, JA
含羞草碱 (MIM) 和阿菲迪霉素 (APH) 是两种常用于基于组织培养的实验中的试剂，以实现 G1 晚期和 S 期的细胞同步。对人类癌细胞系进行 MIM 或 APH 处理后，细胞周期晚期 G1 和 S 期的可逆生长停滞与 p53 和 p21 蛋白水平的适度增加相关。在用任一药物治疗后，观察到 p21 依赖于 p53 和不依赖于 p21 的增加。然而，在化学诱导的同步化后，细胞重新进入细胞周期后的 48 小时内，观察到 p21 蛋白水平显着增加，并且 p53 和 p21 蛋白水平持续升高。此外，通常在用 DNA 损伤剂处理细胞后出现的 p21 蛋白水平增加，而在 MIM 或 APH 同步化后用基因毒性剂处理细胞时，p21 蛋白水平的增加会增强。这些发现表明，在解释使用细胞同步剂的实验结果时应谨慎行事，特别是旨在研究 p53 和 p21 调节途径的研究。
Mimosine (MIM) and aphidicolin (APH) are two agents frequently used in tissue culture-based experiments to achieve cell synchronization at late G1 and S phases. Following MIM or APH treatment of human cancer cell lines, a reversible growth arrest in late G1 and S phases of the cell cycle was correlated with moderate increases in p53 and p21 protein levels. Both p53-dependent and -independent increases in p21 were observed following treatment with either agent. However, a striking increase in p21 protein levels and a continuous elevation in both p53 and p21 protein levels were observed over 48 h after cells re-entered the cell cycle following the chemically-induced synchronization. In addition, the increase in p21 protein levels typically seen following treatment of cells with DNA damaging agents, was enhanced when cells were treated with genotoxic agents following MIM or APH synchronization. These findings suggest that caution should be exercised when interpreting results from experiments using cell synchronization agents, in particular, studies designed to investigate p53- and p21-regulatory pathways.