Nm23-M2/NDP kinase B induces endogenous c-myc and nm23-M1/NDP kinase A overexpression in BAF3 cells. Both NDP kinases protect the cells from oxidative stress-induced death.
The nm23 gene family encodes nucleoside diphosphate kinases (NDPKs) which supply the cell with (d)NTPs. The human NDPKB, also known as the PuF protein, binds the c-myc promoter and transactivates the c-myc protooncogene. We have now studied the effects of mouse NDPKA and NDPKB overexpression on endogenous c-myc transactivation in the mouse BAF3 and the rat PC12 cell lines. c-myc transcripts were found to be up-regulated by NDPKB only in the BAF3 line. This suggests that c-myc transcriptional control via NDPKB depends on the presence of cell-specific co-factors. Unexpectedly, NDPKB also induced NDPKA expression. This new effect was found in both cell lines, suggesting that NDPKB-dependent nm23-M1 gene transactivation requires cis and/or trans elements different from those involved in c-myc transactivation. Moreover, the BAF3 cell proliferation capacities were found to be independent of NDPKA or B cell contents. Interestingly, cell death induced by c-myc overexpression or H(2)O(2) exposure was decreased in nm23-transfected compared to control BAF3 cells. These data collectively suggest that NDPKs might improve cell survival by a mechanism coupling DNA repair and transcriptional regulation of genes involved in DNA damage response.
Arnaud-Dabernat
Sandrine
S
Laboratoire de Biologie de la Différenciation et du Développement, Université Victor Segalen Bordeaux 2, EA 3674, 33076 Bordeaux cedex, France.
Masse
Karine
K
Smani
Moneïm
M
Peuchant
Evelyne
E
Landry
Marc
M
Bourbon
Pierre-Marie
PM
Le Floch
Renaud
R
Daniel
Jean-Yves
JY
Larou
Monique
M
D000818:Animals; D016923:Cell Death; D002460:Cell Line; D049109:Cell Proliferation; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase / Q000235:genetics / Q000502:physiology*; D018384:Oxidative Stress; D020011:Protective Agents; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection
C489428:Myc protein, mouse; D054778:NM23 Nucleoside Diphosphate Kinases; D020011:Protective Agents; D016271:Proto-Oncogene Proteins c-myc; D015534:Trans-Activators; D006861:Hydrogen Peroxide; C517938:NME1 protein, human; C517939:Nme1 protein, mouse; D009701:Nucleoside-Diphosphate Kinase