Sasvári-Székely M, Spasokoukotskaja T, Szóke M, Csapó Z, Turi A, Szántó I, Eriksson S, Staub M
Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis Medical University, Budapest, Hungary.
Biochem Pharmacol. 1998 Nov 1;56(9):1175-9. doi: 10.1016/s0006-2952(98)00108-7.
Deoxycytidine kinase (dCK, EC.2.7.1.74), a key enzyme in intracellular metabolism of many antileukemic drugs, was shown to be activated during treatment of lymphocytes by 2-chloro-2'-deoxyadenosine (Cl-dAdo, cladribine), a potent inhibitor of DNA synthesis. While 5-[3H]-thymidine (TdR) incorporation into DNA was decreased by 80-90%, dCK activity was doubled as a consequence of incubating the cells with 1 microM 2-chloro-2'-deoxyadenosine. Thymidine kinase (dTK, EC.2.7.1.21) activity was slightly decreased under the same conditions, similarly to 5-[3H]-thymidine incorporation. dCK activation could not be prevented by cycloheximide, and neither the amount of dCK protein nor its mRNA level was increased after 2-chloro-2'-deoxyadenosine treatment. These results suggest a post-translational activation of dCK protein during inhibition of DNA synthesis.
脱氧胞苷激酶（dCK，EC.2.7.1.74）是许多抗白血病药物细胞内代谢的关键酶，在淋巴细胞用2-氯-2'-脱氧腺苷（Cl-dAdo，克拉屈滨）治疗期间被激活，Cl-dAdo是一种有效的DNA合成抑制剂。当5-[3H]-胸苷（TdR）掺入DNA减少80 - 90%时，由于用1微摩尔2-氯-2'-脱氧腺苷孵育细胞，dCK活性增加了一倍。在相同条件下，胸苷激酶（dTK，EC.2.7.1.21）活性略有下降，类似于5-[3H]-胸苷掺入情况。放线菌酮不能阻止dCK激活，2-氯-2'-脱氧腺苷处理后dCK蛋白量及其mRNA水平均未增加。这些结果表明在DNA合成抑制过程中dCK蛋白存在翻译后激活。
