The Role of Deoxycytidine Kinase (dCK) in Radiation-Induced Cell Death
AbstractDeoxycytidine kinase (dCK) is a key enzyme in deoxyribonucleoside salvage and the anti-tumor activity for many nucleoside analogs. dCK is activated in response to ionizing radiation (IR)-induced DNA damage and it is phosphorylated on Serine 74 by the Ataxia-Telangiectasia Mutated (ATM) kinase in order to activate the cell cycle G2/M checkpoint. However, whether dCK plays a role in radiation-induced cell death is less clear. In this study, we genetically modified dCK expression by knocking down or expressing a WT (wild-type), S74A (abrogates phosphorylation) and S74E (mimics phosphorylation) of dCK. We found that dCK could decrease IR-induced total cell death and apoptosis. Moreover, dCK increased IR-induced autophagy and dCK-S74 is required for it. Western blotting showed that the ratio of phospho-Akt/Akt, phospho-mTOR/mTOR, phospho-P70S6K/P70S6K significantly decreased in dCK-WT and dCK-S74E cells than that in dCK-S74A cells following IR treatment. Reciprocal experiment by co-immunoprecipitation showed that mTOR can interact with wild-type dCK. IR increased polyploidy and decreased G2/M arrest in dCK knock-down cells as compared with control cells. Taken together, phosphorylated and activated dCK can inhibit IR-induced cell death including apoptosis and mitotic catastrophe, and promote IR-induced autophagy through PI3K/Akt/mTOR pathway. View Full-Text
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Zhong, R.; Xin, R.; Chen, Z.; Liang, N.; Liu, Y.; Ma, S.; Liu, X. The Role of Deoxycytidine Kinase (dCK) in Radiation-Induced Cell Death. Int. J. Mol. Sci. 2016, 17, 1939.
Zhong R, Xin R, Chen Z, Liang N, Liu Y, Ma S, Liu X. The Role of Deoxycytidine Kinase (dCK) in Radiation-Induced Cell Death. International Journal of Molecular Sciences. 2016; 17(11):1939.Chicago/Turabian Style
Zhong, Rui; Xin, Rui; Chen, Zongyan; Liang, Nan; Liu, Yang; Ma, Shumei; Liu, Xiaodong. 2016. "The Role of Deoxycytidine Kinase (dCK) in Radiation-Induced Cell Death." Int. J. Mol. Sci. 17, no. 11: 1939.
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