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首页> 外文期刊>Cell cycle >Ectopic expression of human Cdk2 and its yeast homolog, Ime2, is deleterious to Saccharomyces cerevisiae.
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Ectopic expression of human Cdk2 and its yeast homolog, Ime2, is deleterious to Saccharomyces cerevisiae.

机译：人Cdk2及其酵母同系物Ime2的异位表达对啤酒酵母有害。

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摘要

Entry into and precise progression through the cell cycle depends on the sequential expression and activation of cyclin dependent kinases (CDK). In accord, CDK dysregulation is a hallmark of many cancers. The function of Cdk2 is still an enigma as in vitro studies revealed that it is required for S phase-entry, whereas in vivo studies showed that Cdk2 is not an essential gene. Moreover, unlike other Cdks, or its cyclin E regulator, Cdk2-overexpressing tumors were reported only in one type of tumor. In this report we used budding yeast as a tool to explore Cdk2 function. We showed that hCdk2 promoted S phase in cells carrying a temperature-sensitive mutation in yCDK1, albeit, only when expressed at low or moderate levels. Overexpression of hCdk2 resulted in a defect in the G1 to S transition and a reduction in viability. The same phenotypes were observed in cells overexpressing its yeast functional homolog, Ime2, which is a meiosis-specific CDK-like kinase. A genetic interaction with the DNA damage checkpoint was demonstrated by showing an increased toxicity of hCdk2 and Ime2 in RAD53-deleted cells, and delayed Rad53 activation in response to MMS treatment in cells overexpressing hCdk2 or Ime2.
机译：细胞周期的进入和精确进展取决于细胞周期蛋白依赖性激酶（CDK）的顺序表达和激活。因此，CDK失调是许多癌症的标志。 Cdk2的功能仍然是一个谜，因为体外研究表明Cdk2是S期进入所必需的，而体内研究表明Cdk2不是必需的基因。此外，与其他Cdks或其细胞周期蛋白E调节剂不同，仅在一种类型的肿瘤中报告过表达Cdk2的肿瘤。在本报告中，我们使用发芽酵母作为探索Cdk2功能的工具。我们显示，hCdk2可以在yCDK1中携带温度敏感突变的细胞中促进S期，尽管只有在低或中等水平表达时才如此。 hCdk2的过表达导致从G1到S的转变中的缺陷，并降低了生存能力。在过表达其酵母功能同源物Ime2的细胞中观察到相同的表型，Ime2是减数分裂特异性CDK样激酶。通过显示在RAD53缺失的细胞中hCdk2和Ime2的毒性增加，并在过表达hCdk2或Ime2的细胞中响应MMS处理而延迟了Rad53活化，证明了与DNA损伤检查点的遗传相互作用。

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