A novel human nucleoside diphosphate (NDP) kinase, Nm23-H6, localizes in mitochondria and affects cytokinesis

Nucleoside diphosphate kinases (NDP kinases) are enzymes known to be conser ved throughout evolution and have been shown to be involved in various biol ogical events, in addition to the "housekeeping" phosphotransferase activit y. We present the molecular cloning-of a novel human NDP kinase gene, terme d Nm23-H6. Nm23-H6 gene has been mapped at chromosome 3p21.3 and is highly expressed in heart, placenta, skeletal muscle, and some of the cancer cell lines. Recombinant Nm23-H6 protein has been identified to exhibit functiona l NDP kinase activity. Immunolocalization studies showed that both endogeno us and inducibly expressed Nm23-H6 proteins were present as short, filament -like, perinuclear radical arrays and that they colocalized with mitochondr ia. Cell fractionation study also demonstrated the presence of Nm23-H6 prot ein in a mitochondria-rich fraction. Moreover, induction of overexpression of Nm23-H6 in SAOS2 cells, using the Cre-loxP gene activation system, resul ted in growth suppression and generation of multinucleated cells. Flow cyto metric analysis also demonstrated that the proportion of cells with more th an 4N DNA content increased to 28.1% after induction of Nm23-H6, coinciding with the appearance of multinucleated cells. These observations suggest th at Nm23-H6, a new member of the NDP kinase family, resides in mitochondria and plays a role in regulation of cell growth and cell cycle progression. ( C) 1999 Wiley-Liss, Inc.