Csapó Z, Sasvári-Székely M, Spasokoukotskaja T, Staub M
Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary.
Acta Biochim Pol. 2001;48(1):251-6.
Deoxycytidine kinase (dCK) is one of the key enzymes of deoxynucleoside salvage supplying resting lymphocytes with DNA precursors for synthesis and repair. The level of dCK activity is especially important in chemotherapy with the use of deoxynucleoside analogues like arabinosyl cytosine (Citarabid, ara-C), or 2-chloro-deoxyadenosine (Cladribine, CdA). Previous results showed that Cladribine treatment of human lymphocytes increased several fold the activity of dCK without increasing the amount of dCK protein itself (Sasvári-Székely, et al., 1998, Biochem. Pharmacol. 56, 1175), and a possible post-translational modification was suggested. This theory was further investigated using NaF as an inhibitor of protein phosphatases. It was shown that NaF treatment of cells elevated dCK activity while inhibiting DNA synthesis. The possible mechanism of dCK activation/inactivation induced by exposure of cell cultures to different agents is discussed.
脱氧胞苷激酶（dCK）是脱氧核苷补救途径的关键酶之一，为静止淋巴细胞提供用于DNA合成和修复的前体物质。在使用脱氧核苷类似物如阿糖胞苷（赛德萨，ara-C）或2-氯脱氧腺苷（克拉屈滨，CdA）进行化疗时，dCK活性水平尤为重要。先前的研究结果表明，用克拉屈滨处理人淋巴细胞可使dCK活性提高数倍，而dCK蛋白本身的量并未增加（萨斯瓦里-塞凯利等人，1998年，《生物化学与药理学》56卷，第1175页），并提出了一种可能的翻译后修饰。本研究使用氟化钠作为蛋白磷酸酶抑制剂对该理论进行了进一步探究。结果表明，用氟化钠处理细胞可提高dCK活性，同时抑制DNA合成。本文讨论了细胞培养物暴露于不同试剂所诱导的dCK激活/失活的可能机制。
