NM23 NUCLEOSIDE DIPHOSPHATE KINASE - TOWARD A STRUCTURAL AND BIOCHEMICAL UNDERSTANDING OF ITS BIOLOGICAL FUNCTIONS

The nm23 gene, a putative metastasis suppressor gene, was originally i dentified by its reduced expression in highly metastatic K-1735 murine melanoma cell lines, as compared to related, low metastatic melanoma cell lines, Transfection of nm23 cDNA has been reported to suppress ma lignant progression in Drosophila and mammalian cells. Highly conserve d homologues of nm23 have been found in organisms ranging from the pro karyote Myxococcus xanthus to Drosophila, where the gene is involved i n normal development and differentiation. The product of the nm23 gene exhibits a nucleoside diphosphate kinase activity, yet the nucleoside diphosphate kinase activity of Nm23 does not correlate with its appar ent biological functions. We review recent cellular, genetic, biochemi cal and Xray crystallographic data to formulate and evaluate hypothese s concerning the molecular mechanism of nm23 action.