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

• Published in: Experimental cell research 2004-12, Vol.301 (2), p.293-304
• Main Authors: Arnaud-Dabernat, Sandrine, Masse, Karine, Smani, Moneïm, Peuchant, Evelyne, Landry, Marc, Bourbon, Pierre-Marie, Le Floch, Renaud, Daniel, Jean-Yves, Larou, Monique
• Format: Article
• Language: English
• Subjects: Animals; BAF3 cells; c- myc; Cell Death; Cell Line; Cell Proliferation; Hydrogen Peroxide - pharmacology; Induced cell death; Mice; nm23; NM23 Nucleoside Diphosphate Kinases; Nucleoside-Diphosphate Kinase - genetics; Nucleoside-Diphosphate Kinase - physiology; Oxidative Stress; Protective Agents; Proto-Oncogene Proteins c-myc - biosynthesis; Proto-Oncogene Proteins c-myc - physiology; Trans-Activators - physiology; Transcriptional Activation; Transfection
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2004.07.026

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 2O 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.