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In Vivo Analysis of Drosophila Deoxyribonucleoside Kinase Function in Cell Cycle, Cell Survival and Anti-Cancer Drugs Resistance

In Vivo Analysis of Drosophila Deoxyribonucleoside Kinase Function in Cell Cycle, Cell Survival... In vitro studies have shown that Drosophila melanogaster has a highly efficient singledeoxyribonucleoside kinase (dNK) multisubstrate enzyme. dNK is related to the mammalianThymidine Kinase 2 (TK2) group involved in the nucleotide synthesis salvage pathway. To study thedNK function in vivo, we constructed transgenic Drosophila strains and impaired the nucleotide denovo synthesis pathway, using antifolates such as aminopterin. Our results show that dNK overexpressionrescues both cell death and cell cycle arrest triggered by this anti-cancer drug, and confersglobal resistance on the fly. Moreover, we show that fly viability and growth depend on the exquisiteratio between dNK expression and its substrate thymidine (dT) in the medium, and that increased dTconcentrations 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 thedE2F1 transcription factor involved in the G1/S transition. dNK is therefore functionally more closelyrelated to mammalian TK1 than to TK2. This strongly suggest that dNK plays a role in cellproliferation in physiological conditions. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cell Cycle Taylor & Francis

In Vivo Analysis of Drosophila Deoxyribonucleoside Kinase Function in Cell Cycle, Cell Survival and Anti-Cancer Drugs Resistance

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References (45)

Publisher
Taylor & Francis
Copyright
Copyright © 2006 Landes Bioscience
ISSN
1551-4005
eISSN
1538-4101
DOI
10.4161/cc.5.7.2613
pmid
16582629
Publisher site
See Article on Publisher Site

Abstract

In vitro studies have shown that Drosophila melanogaster has a highly efficient singledeoxyribonucleoside kinase (dNK) multisubstrate enzyme. dNK is related to the mammalianThymidine Kinase 2 (TK2) group involved in the nucleotide synthesis salvage pathway. To study thedNK function in vivo, we constructed transgenic Drosophila strains and impaired the nucleotide denovo synthesis pathway, using antifolates such as aminopterin. Our results show that dNK overexpressionrescues both cell death and cell cycle arrest triggered by this anti-cancer drug, and confersglobal resistance on the fly. Moreover, we show that fly viability and growth depend on the exquisiteratio between dNK expression and its substrate thymidine (dT) in the medium, and that increased dTconcentrations 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 thedE2F1 transcription factor involved in the G1/S transition. dNK is therefore functionally more closelyrelated to mammalian TK1 than to TK2. This strongly suggest that dNK plays a role in cellproliferation in physiological conditions.

Journal

Cell Cycle – Taylor & Francis

Published: Apr 1, 2006

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