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

Authors

  • Hiromasa Tsuiki,

    1. Department of Tumor Genetics and Biology, Kumamoto University School of Medicine, Kumamoto 860–0811, Japan
    2. Department of Neurosurgery, Kumamoto University School of Medicine, Kumamoto 860–0811, Japan
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  • Masayuki Nitta,

    1. Department of Tumor Genetics and Biology, Kumamoto University School of Medicine, Kumamoto 860–0811, Japan
    2. Department of Neurosurgery, Kumamoto University School of Medicine, Kumamoto 860–0811, Japan
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  • Akiko Furuya,

    1. Tokyo Research Laboratories, Kyowa Hakko Kogyo Co. Ltd., Machida, Tokyo 194–8533, Japan
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  • Nobuo Hanai,

    1. Tokyo Research Laboratories, Kyowa Hakko Kogyo Co. Ltd., Machida, Tokyo 194–8533, Japan
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  • Toshiyoshi Fujiwara,

    1. First Department of Surgery, Okayama University Medical School, Okayama 700–0914, Japan
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  • Masaki Inagaki,

    1. Department of Biochemistry, Aichi Cancer Research Institute, 1–1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464–0021, Japan
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  • Masato Kochi,

    1. Department of Neurosurgery, Kumamoto University School of Medicine, Kumamoto 860–0811, Japan
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  • Yukitaka Ushio,

    1. Department of Neurosurgery, Kumamoto University School of Medicine, Kumamoto 860–0811, Japan
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  • Hideyuki Saya,

    1. Department of Tumor Genetics and Biology, Kumamoto University School of Medicine, Kumamoto 860–0811, Japan
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  • Hideo Nakamura

    Corresponding author
    1. Department of Tumor Genetics and Biology, Kumamoto University School of Medicine, Kumamoto 860–0811, Japan
    2. Department of Neurosurgery, Kumamoto University School of Medicine, Kumamoto 860–0811, Japan
    • Department of Tumor Genetics and Biology, Kumamoto University School of Medicine, 2–2-1 Honjo, Kumamoto 860–0811, Japan.
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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. J. Cell. Biochem. 76:254–269, 1999. © 1999 Wiley-Liss, Inc.

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