CELL LINE-SPECIFIC DIFFERENCES IN THE CONTROL OF CELL-CYCLE PROGRESSION IN THE ABSENCE OF MITOSIS

CELL LINE-SPECIFIC DIFFERENCES IN THE CONTROL OF CELL-CYCLE PROGRESSION IN THE ABSENCE OF MITOSIS
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DOI:
10.1073/pnas.87.24.9553
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发表时间:
1990-12-01
影响因子:
11.1
通讯作者:
SCHIMKE, RT
SCHIMKE, RT
中科院分区:
综合性期刊1区
文献类型:
--
作者:
KUNG, AL;SHERWOOD, SW;SCHIMKE, RT

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本文报道了哺乳动物细胞系在用破坏有丝分裂纺锤体组装的药物(Colcemid、nocodazo和紫杉醇)抑制有丝分裂时进入后续细胞周期的倾向方面存在重大差异。人类HeLa S3细胞代表一个极端,仍然处于有丝分裂停滞状态,细胞周期蛋白B和p34cdc2激酶活性水平升高。在中国仓鼠卵巢细胞中,只有在没有有丝分裂的情况下,细胞周期蛋白B水平和p34cdc2激酶活性的周期性上升和下降才被暂时抑制。细胞进入随后的细胞周期,没有分裂,导致细胞DNA含量连续加倍。一般来说,在没有有丝分裂的情况下进入后续细胞周期的倾向似乎与物种有关,这样人类细胞系就会永久地处于有丝分裂状态,而啮齿动物细胞系只有在纺锤体组装被破坏时才会暂时被抑制。我们对这些结果的解读表明,在哺乳动物细胞系中,存在一个检查点,该检查点用于连接到细胞周期进程,直到完成某些核动力学事件。此外,在一些细胞系中存在这样的检查点,而在另一些细胞系中不存在,或者控制机制的严密性在不同的细胞系中有所不同。
This paper reports that there are major differences between mammalian cell lines in the propensity to progress into subsequent cell cycles when mitosis is inhibited with agents that disrupt the assembly of the mitotic spindle apparatus (Colcemid, nocodazole, and taxol). Human HeLa S3 cells, which represent one extreme, remain arrested in mitosis, with elevated levels of cyclin B and p34cdc2 kinase activity. In Chinese hamster ovary cells, at the other extreme, the periodic rise and fall of cyclin B levels and p34cdc2 kinase activity is only transiently inhibited in the absence of mitosis. The cells progress into subsequent cell cycles, without dividing, resulting in serial doublings of cellular DNA content. In general, the propensity to progress into subsequent cell cycles in the absence of mitosis appears to be species related, such that human cell lines remain permanently blocked in a mitotic state, whereas rodent cell lines are only transiently inhibited when spindle assembly is disrupted. We interpret these results to indicate that in mammalian cell lines there exists a checkpoint which serves to couple to cell cycle progression to the completion of certain karyokinetic events. Furthermore, either such a checkpoint exists in some cell lines but not in others or the stringency of the control mechanism varies among different cell lines.