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首页> 外文期刊>Cell cycle >In vivo analysis of Drosophila deoxyribonucleoside kinase function in cell cycle, cell survival and anti-cancer drugs resistance.
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In vivo analysis of Drosophila deoxyribonucleoside kinase function in cell cycle, cell survival and anti-cancer drugs resistance.

机译：果蝇脱氧核糖核苷激酶在细胞周期，细胞存活和抗癌药耐药性方面的体内分析。

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摘要

In vitro studies have shown that Drosophila melanogaster has a highly efficient single deoxyribonucleoside kinase (dNK) multisubstrate enzyme. dNK is related to the mammalian Thymidine Kinase 2 (TK2) group involved in the nucleotide synthesis salvage pathway. To study the dNK function in vivo, we constructed transgenic Drosophila strains and impaired the nucleotide de novo synthesis pathway, using antifolates such as aminopterin. Our results show that dNK overexpression rescues both cell death and cell cycle arrest triggered by this anti-cancer drug, and confers global resistance on the fly. Moreover, we show that fly viability and growth depend on the exquisite ratio between dNK expression and its substrate thymidine (dT) in the medium, and that increased dT concentrations trigger apoptosis and a decrease in body mass when dNK is mis-expressed. Finally, dNK expression, unlike that of TK2, is cell cycle dependent and under the control of CyclinE and the dE2F1 transcription factor involved in the G1/S transition. dNK is therefore functionally more closely related to mammalian TK1 than to TK2. This strongly suggests that dNK plays a role in cell proliferation in physiological conditions.
机译：体外研究表明，果蝇具有高效的单个脱氧核糖核苷激酶（dNK）多底物酶。 dNK与参与核苷酸合成挽救途径的哺乳动物胸苷激酶2（TK2）组有关。为了研究体内dNK的功能，我们构建了转基因果蝇菌株，并使用抗叶酸剂（如氨基蝶呤）破坏了核苷酸的从头合成途径。我们的结果表明，dNK的过表达可以挽救这种抗癌药触发的细胞死亡和细胞周期停滞，并实时赋予全球抵抗力。此外，我们表明果蝇的生存能力和生长取决于培养基中dNK表达与其底物胸苷（dT）的精确比率，并且当dNK表达错误时，增加的dT浓度会触发细胞凋亡并降低体重。最后，与TK2不同，dNK表达是细胞周期依赖性的，并受CyclinE和参与G1 / S过渡的dE2F1转录因子的控制。因此，dNK在功能上与哺乳动物TK1的关系比与TK2的关系更紧密。这强烈暗示了dNK在生理条件下在细胞增殖中起作用。

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