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Int. J. Mol. Sci. 2016, 17(11), 1939; doi:10.3390/ijms17111939

The Role of Deoxycytidine Kinase (dCK) in Radiation-Induced Cell Death

1
Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Changchun 130021, China
2
Department Radiology, the 2st Hospitals Affiliated to Jilin University, Changchun 130021, China
3
Department Diagnostic Imaging, Weihai Chest Hospital, Weihai 264220, China
4
Department Radiation Oncology, the 2nd Hospitals Affiliated to Jilin University, Changchun 130021, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Anthony Lemarié
Received: 22 August 2016 / Revised: 12 October 2016 / Accepted: 14 November 2016 / Published: 21 November 2016
(This article belongs to the Collection Programmed Cell Death and Apoptosis)
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Abstract

Deoxycytidine 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
Keywords: deoxycytidine kinase (dCK); autophagy; apoptosis; mitotic catastrophe; radiation deoxycytidine kinase (dCK); autophagy; apoptosis; mitotic catastrophe; radiation
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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.

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