TRANSCRIPTION EFFECT OF NM23-M2 NDP KINASE ON C-MYC ONCOGENE/

Transactivating factor PuF which interacts with a nuclease hypersensit ive element locates upstream from the c-myc gene. PuF was recently ide ntified as being encoded by nm23-H2/NDP kinase gene [Postel, E. H., Be rberich, S. J., Flint, S. J., and Ferrone, C. A. (1993) Science 261, 4 28-429]. Here we have studied the correlation of expression between c- myc and nm23 genes in vitro. By a comparative study of the expression of 2 genes in cell lines, no direct correlation of kinetics was found. A plasmid containing the human c-myc fragment (c-myc CAT) was cloned upstream from the bacterial chloramphenicol acetyltransferase (CAT) ge ne. When the murine melanoma cell line was cotransfected with a nm23-M 2/NDP kinase expression vector and c-myc CAT, CAT activity was elevate d. In addition, cell cycle phases in the murine cell lines transfected with nm23/NDP kinase were estimated; an alteration of the cell cycle, prolonged S-phase was found in the cell lines transfected with nm23-M 2/NDP kinase, whereas human nm23-H2/NDP kinase did not play a role in transactivating the c-myc gene or in S-phase prolongation in murine ce ll lines. From these results we conclude that the murine nm23-M2 gene transactivates the c-myc gene and controls the cell cycle, S-phase, in directly via a cellular cofactor in the murine cell line, which does n ot work with the human nm23-H2 gene.