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

Hiromasa Tsuiki, Masayuki Nitta, Akiko Furuya, Nobuo Hanai, Toshiyoshi Fujiwara, Masaki Inagaki, Masato Kochi, Yukitaka Ushio, Hideyuki Saya, Hideo Nakamura

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65 Citations (Scopus)

Abstract

Nucleoside diphosphate kinases (NDP kinases) are enzymes known to be conserved throughout evolution and have been shown to be involved in various biological events, in addition to the 'housekeeping' phosphotransferase activity. We present the molecular cloning of a novel human NDP kinase gene, termed 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 functional NDP kinase activity. Immunolocalization studies showed that both endogenous and inducibly expressed Nm23-H6 proteins were present as short, filament-like, perinuclear radical arrays and that they colocalized with mitochondria. Cell fractionation study also demonstrated the presence of Nm23-H6 protein in a mitochondria- rich fraction. Moreover, induction of overexpression of Nm23-H6 in SAOS2 cells, using the Cre-loxP gene activation system, resulted in growth suppression and generation of multinucleated cells. Flow cytometric analysis also demonstrated that the proportion of cells with more than 4N DNA content increased to 28.1% after induction of Nm23-H6, coinciding with the appearance of multinucleated cells. These observations suggest that 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.

Original languageEnglish
Pages (from-to)254-269
Number of pages16
JournalJournal of Cellular Biochemistry
Volume76
Issue number2
DOIs
Publication statusPublished - 1999

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Keywords

  • 3p21.3
  • Cre-mediated gene activation system
  • Mitochondria
  • Multinucleated cells
  • NDP kinase

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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