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In vivo analysis of Drosophila deoxyribonucleoside kinase function in cell cycle, cell survival and anti-cancer drugs resistance

Legent, K ; Mas, M ; Dutriaux, A ; Bertrandy, S ; Flagiello, D ; Delanoue, R ; Piskur, Jure LU and Silber, J (2006) In Cell Cycle 5(7). p.740-749
Abstract
In vitro studies have shown that Drosophila melanogaster has a highly efficient single deoxyribonucleoside kinase (dNK) multisubstrate enzyme. dNK is related to the mammalian Thymidine Kinase 2 (TK2) group involved in the nucleotide synthesis salvage pathway. To study the dNK function in vivo, we constructed transgenic Drosophila strains and impaired the nucleotide de novo synthesis pathway, using antifolates such as aminopterin. Our results show that dNK overexpression rescues both cell death and cell cycle arrest triggered by this anti-cancer drug, and confers global resistance on the fly. Moreover, we show that fly viability and growth depend on the exquisite ratio between dNK expression and its substrate thymidine (dT) in the medium,... (More)
In vitro studies have shown that Drosophila melanogaster has a highly efficient single deoxyribonucleoside kinase (dNK) multisubstrate enzyme. dNK is related to the mammalian Thymidine Kinase 2 (TK2) group involved in the nucleotide synthesis salvage pathway. To study the dNK function in vivo, we constructed transgenic Drosophila strains and impaired the nucleotide de novo synthesis pathway, using antifolates such as aminopterin. Our results show that dNK overexpression rescues both cell death and cell cycle arrest triggered by this anti-cancer drug, and confers global resistance on the fly. Moreover, we show that fly viability and growth depend on the exquisite ratio between dNK expression and its substrate thymidine (dT) in the medium, and that increased dT concentrations 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 the dE2F1 transcription factor involved in the G(1)/S transition. dNK is therefore functionally more closely related to mammalian TK1 than to TK2. This strongly suggests that dNK plays a role in cell proliferation in physiological conditions. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
dE2F1, growth, apoptosis, antifolate resistance, dNK, Drosophila, deoxyribonucleoside kinase, proliferation
in
Cell Cycle
volume
5
issue
7
pages
740 - 749
publisher
Landes Bioscience
external identifiers
  • wos:000238282900016
  • pmid:16582629
  • scopus:33645702188
ISSN
1551-4005
language
English
LU publication?
yes
id
fd67f471-f781-4279-9def-8507f08a2d06 (old id 406227)
alternative location
http://www.landesbioscience.com/journals/cc/article/2613
date added to LUP
2016-04-01 12:22:01
date last changed
2021-02-17 06:48:25
@article{fd67f471-f781-4279-9def-8507f08a2d06,
  abstract     = {In vitro studies have shown that Drosophila melanogaster has a highly efficient single deoxyribonucleoside kinase (dNK) multisubstrate enzyme. dNK is related to the mammalian Thymidine Kinase 2 (TK2) group involved in the nucleotide synthesis salvage pathway. To study the dNK function in vivo, we constructed transgenic Drosophila strains and impaired the nucleotide de novo synthesis pathway, using antifolates such as aminopterin. Our results show that dNK overexpression rescues both cell death and cell cycle arrest triggered by this anti-cancer drug, and confers global resistance on the fly. Moreover, we show that fly viability and growth depend on the exquisite ratio between dNK expression and its substrate thymidine (dT) in the medium, and that increased dT concentrations 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 the dE2F1 transcription factor involved in the G(1)/S transition. dNK is therefore functionally more closely related to mammalian TK1 than to TK2. This strongly suggests that dNK plays a role in cell proliferation in physiological conditions.},
  author       = {Legent, K and Mas, M and Dutriaux, A and Bertrandy, S and Flagiello, D and Delanoue, R and Piskur, Jure and Silber, J},
  issn         = {1551-4005},
  language     = {eng},
  number       = {7},
  pages        = {740--749},
  publisher    = {Landes Bioscience},
  series       = {Cell Cycle},
  title        = {In vivo analysis of Drosophila deoxyribonucleoside kinase function in cell cycle, cell survival and anti-cancer drugs resistance},
  url          = {http://www.landesbioscience.com/journals/cc/article/2613},
  volume       = {5},
  year         = {2006},
}