Escalas N, Davezac N, De Rycke J, Baldin V, Mazars R, Ducommun B
LBCMCP-CNRS, Université Paul Sabatier, Toulouse, France.
Exp Cell Res. 2000 May 25;257(1):206-12. doi: 10.1006/excr.2000.4878.
HeLa cells exposed to Escherichia coli cytolethal distending toxins (CDT) arrest their cell cycle at the G2/M transition. We have shown previously that in these cells the CDK1/cyclin B complex is inactive and can be reactivated in vitro using recombinant CDC25 phosphatase. Here we have investigated in vivo the effects of CDC25 on this cell cycle checkpoint. We report that overexpression of CDC25B or CDC25C overrides an established CDT-induced G2 cell cycle arrest and leads the cells to accumulate in an abnormal mitotic stage with condensed chromatin and high CDK1 activity. This effect can be counteracted by coexpression of the WEE1 kinase. In contrast, overexpression of CDC25B or C prior to CDT treatment prevents G2 arrest and allows most of the cells to progress through mitosis with only a low percentage of cells arrested in abnormal mitosis. The implications of these results on the biochemical nature of the CDT-induced cell cycle arrest are discussed.
暴露于大肠杆菌细胞致死性膨胀毒素（CDT）的HeLa细胞在G2/M期转换时停滞其细胞周期。我们之前已经表明，在这些细胞中，CDK1/细胞周期蛋白B复合物无活性，并且可以使用重组CDC25磷酸酶在体外重新激活。在这里，我们在体内研究了CDC25对这个细胞周期检查点的影响。我们报告说，CDC25B或CDC25C的过表达克服了已建立的CDT诱导的G2细胞周期停滞，并导致细胞在具有浓缩染色质和高CDK1活性的异常有丝分裂阶段积累。这种效应可以通过共表达WEE1激酶来抵消。相反，在CDT处理之前过表达CDC25B或C可防止G2期停滞，并使大多数细胞通过有丝分裂，只有低百分比的细胞停滞在异常有丝分裂中。讨论了这些结果对CDT诱导的细胞周期停滞的生化性质的影响。
