Molecular and Cellular Biochemistry

, Volume 329, Issue 1–2, pp 51–62 | Cite as

The mammalian Nm23/NDPK family: from metastasis control to cilia movement

  • Mathieu Boissan
  • Sandrine Dabernat
  • Evelyne Peuchant
  • Uwe Schlattner
  • Ioan Lascu
  • Marie-Lise LacombeEmail author


Nucleoside diphosphate kinases (NDPK) are encoded by the NME genes, also called NM23. They catalyze the transfer of γ-phosphate from nucleoside triphosphates to nucleoside diphosphates by a ping-pong mechanism involving the formation of a high energy phospho-histidine intermediate [1, 2]. Besides their known functions in the control of intracellular nucleotide homeostasis, they are involved in multiple physiological and pathological cellular processes such as differentiation, development, metastastic dissemination or cilia functions. Over the past 15 years, ten human genes have been discovered encoding partial, full length, and/or tandemly repeated Nm23/NDPK domains, with or without N-or C-terminal extensions and/or additional domains. These genes encode proteins exhibiting different functions at various tissular and subcellular localizations. Most of these genes appear late in evolution with the emergence of the vertebrate lineage. This review summarizes the present knowledge on these multitalented proteins.


Nucleoside diphosphate kinase Signaling Cancer Mitochondria Phospholipid 



The authors are greatly indebted to Pr. J. Y. Daniel, who created the first NM23 transgenic mice, for his continued interest in these works. We thank Yves Chrétien for assistance in figure preparation and C. Mailleau for technical assistance. This work was supported by the Germaine de Stael program for Franco-Swiss collaboration (U.S.; M.L.L.), the Agence Nationale de la Recherche (chaire d’excellence to U.S.), the Institut National de la Santé et de la Recherche Médicale (INSERM) and grants (to M.L.L.) from the Groupement des Entreprises Françaises contre le Cancer (GEFLUC) and from the Association pour la Recherche contre le Cancer (ARC).


  1. 1.
    Cleland WW (1963) The kinetics of enzyme-catalyzed reactions with two or more substrates or products. III. Prediction of initial velocity and inhibition patterns by inspection. Biochim Biophys Acta 67:188–196. doi: 10.1016/0006-3002(63)91816-X PubMedCrossRefGoogle Scholar
  2. 2.
    Norman AW, Wedding RT, Black MK (1965) Detection of phosphohistidine in nucleoside diphosphokinase isolated from Jerusalem artichoke mitochondria. Biochem Biophys Res Commun 20:703–709. doi: 10.1016/0006-291X(65)90073-2 PubMedCrossRefGoogle Scholar
  3. 3.
    Yamagata K, Oda N, Kaisaki PJ, Menzel S, Furuta H, Vaxillaire M, Southam L, Cox RD, Lathrop GM, Boriraj VV, Chen X, Cox NJ, Oda Y, Yano H, Le Beau MM, Yamada S, Nishigori H, Takeda J, Fajans SS, Hattersley AT, Iwasaki N, Hansen T, Pedersen O, Polonsky KS, Turner RC, Velho G, Chevre JC, Froguel P, Bell GI (1996) Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset diabetes of the young (MODY3). Nature 384:455–458. doi: 10.1038/384455a0 PubMedCrossRefGoogle Scholar
  4. 4.
    Lacombe ML, Milon L, Munier A, Mehus JG, Lambeth DO (2000) The human Nm23/nucleoside diphosphate kinases. J Bioenerg Biomembr 32:247–258. doi: 10.1023/A:1005584929050 PubMedCrossRefGoogle Scholar
  5. 5.
    Tsuiki H, Nitta M, Furuya A, Hanai N, Fujiwara T, Inagaki M, Kochi M, Ushio Y, Saya H, Nakamura H (1999) A novel human nucleoside diphosphate (NDP) kinase, Nm23-H6, localizes in mitochondria and affects cytokinesis. J Cell Biochem 76:254–269. doi: 10.1002/(SICI)1097-4644(20000201)76:2<254::AID-JCB9>3.0.CO;2-G PubMedCrossRefGoogle Scholar
  6. 6.
    Dereeper A, Guignon V, Blanc G, Audic S, Buffet S, Chevenet F, Dufayard JF, Guindon S, Lefort V, Lescot M, Claverie JM, Gascuel O (2008) robust phylogenetic analysis for the non-specialist. Nucleic Acids Res 36:W465–W469. doi: 10.1093/nar/gkn180 PubMedCrossRefGoogle Scholar
  7. 7.
    Steeg PS, Bevilacqua G, Kopper L, Thorgeirsson UP, Talmadge JE, Liotta LA, Sobel ME (1988) Evidence for a novel gene associated with low tumor metastatic potential. J Natl Cancer Inst 80:200–204. doi: 10.1093/jnci/80.3.200 PubMedCrossRefGoogle Scholar
  8. 8.
    Steeg PS (2006) Tumor metastasis: mechanistic insights and clinical challenges. Nat Med 12:895–904. doi: 10.1038/nm1469 PubMedCrossRefGoogle Scholar
  9. 9.
    Ni X, Gu S, Dai J, Cheng H, Guo L, Li L, Ji C, Xie Y, Ying K, Mao Y (2003) Isolation and characterization of a novel human NM23-H1B gene, a different transcript of NM23-H1. J Hum Genet 48:96–100. doi: 10.1007/s100380300014 PubMedCrossRefGoogle Scholar
  10. 10.
    Valentijn LJ, Koster J, Versteeg R (2006) Read-through transcript from NM23-H1 into the neighboring NM23-H2 gene encodes a novel protein, NM23-LV. Genomics 87:483–489. doi: 10.1016/j.ygeno.2005.11.004 PubMedCrossRefGoogle Scholar
  11. 11.
    Venturelli D, Martinez R, Melotti P, Casella I, Peschle C, Cucco C, Spampinato G, Darzynkiewicz Z, Calabretta B (1995) Overexpression of DR-nm23, a protein encoded by a member of the nm23 gene family, inhibits granulocyte differentiation and induces apoptosis in 32Dc13 myeloid cells. Proc Natl Acad Sci USA 92:7435–7439. doi: 10.1073/pnas.92.16.7435 PubMedCrossRefGoogle Scholar
  12. 12.
    Amendola R, Martinez R, Negroni A, Venturelli D, Tanno B, Calabretta B, Raschella G (2001) DR-nm23 expression affects neuroblastoma cell differentiation, integrin expression, and adhesion characteristics. Med Pediatr Oncol 36:93–96. doi: 10.1002/1096-911X(20010101)36:1<93::AID-MPO1021>3.0.CO;2-3 PubMedCrossRefGoogle Scholar
  13. 13.
    Negroni A, Venturelli D, Tanno B, Amendola R, Ransac S, Cesi V, Calabretta B, Raschella G (2000) Neuroblastoma specific effects of DR-nm23 and its mutant forms on differentiation and apoptosis. Cell Death Differ 7:843–850. doi: 10.1038/sj.cdd.4400720 PubMedCrossRefGoogle Scholar
  14. 14.
    Milon L, Meyer P, Chiadmi M, Munier A, Johansson M, Karlsson A, Lascu I, Capeau J, Janin J, Lacombe ML (2000) The human nm23-H4 gene product is a mitochondrial nucleoside diphosphate kinase. J Biol Chem 275:14264–14272. doi: 10.1074/jbc.275.19.14264 PubMedCrossRefGoogle Scholar
  15. 15.
    Tokarska-Schlattner M, Boissan M, Munier A, Borot C, Mailleau C, Speer O, Schlattner U, Lacombe ML (2008) The nucleoside diphosphate kinase D (NM23-H4) binds the inner mitochondrial membrane with high affinity to cardiolipin and couples nucleotide transfer with respiration. J Biol Chem 283:26198–26207. doi: 10.1074/jbc.M803132200 PubMedCrossRefGoogle Scholar
  16. 16.
    Postel EH (2003) Multiple biochemical activities of NM23/NDP kinase in gene regulation. J Bioenerg Biomembr 35:31–40. doi: 10.1023/A:1023485505621 PubMedCrossRefGoogle Scholar
  17. 17.
    Fan Z, Beresford PJ, Oh DY, Zhang D, Lieberman J (2003) Tumor suppressor NM23-H1 is a granzyme A-activated DNase during CTL-mediated apoptosis, and the nucleosome assembly protein SET is its inhibitor. Cell 112:659–672. doi: 10.1016/S0092-8674(03)00150-8 PubMedCrossRefGoogle Scholar
  18. 18.
    Kaetzel DM, Zhang Q, Yang M, McCorkle JR, Ma D, Craven RJ (2006) Potential roles of 3′-5′ exonuclease activity of NM23-H1 in DNA repair and malignant progression. J Bioenerg Biomembr 38:163–167. doi: 10.1007/s10863-006-9040-3 PubMedCrossRefGoogle Scholar
  19. 19.
    Engel M, Veron M, Theisinger B, Lacombe ML, Seib T, Dooley S, Welter C (1995) A novel serine/threonine-specific protein phosphotransferase activity of Nm23/nucleoside-diphosphate kinase. Eur J Biochem 234:200–207. doi: 10.1111/j.1432-1033.1995.200_c.x PubMedCrossRefGoogle Scholar
  20. 20.
    Steeg PS, Palmieri D, Ouatas T, Salerno M (2003) Histidine kinases and histidine phosphorylated proteins in mammalian cell biology, signal transduction and cancer. Cancer Lett 190:1–12. doi: 10.1016/S0304-3835(02)00499-8 PubMedCrossRefGoogle Scholar
  21. 21.
    Cuello F, Schulze RA, Heemeyer F, Meyer HE, Lutz S, Jakobs KH, Niroomand F, Wieland T (2003) Activation of heterotrimeric G proteins by a high energy phosphate transfer via nucleoside diphosphate kinase (NDPK) B and Gbeta subunits. Complex formation of NDPK B with Gbeta gamma dimers and phosphorylation of His-266 IN Gbeta. J Biol Chem 278:7220–7226. doi: 10.1074/jbc.M210304200 PubMedCrossRefGoogle Scholar
  22. 22.
    Wieland T (2007) Interaction of nucleoside diphosphate kinase B with heterotrimeric G protein betagamma dimers: consequences on G protein activation and stability. Naunyn Schmiedebergs Arch Pharmacol 374:373–383. doi: 10.1007/s00210-006-0126-6 PubMedCrossRefGoogle Scholar
  23. 23.
    Kimura N (1993) Role of nucleoside diphosphate kinase in G-Protein action. In: Dickey BF, Birnbaumer L (eds) Handbook of experimental pharmacology. Springer-Verlag, New York, pp 485–496Google Scholar
  24. 24.
    Otero AS (2000) NM23/nucleoside diphosphate kinase and signal transduction. J Bioenerg Biomembr 32:269–275. doi: 10.1023/A:1005589029959 PubMedCrossRefGoogle Scholar
  25. 25.
    Tseng YH, Vicent D, Zhu J, Niu Y, Adeyinka A, Moyers JS, Watson PH, Kahn CR (2001) Regulation of growth and tumorigenicity of breast cancer cells by the low molecular weight GTPase Rad and nm23. Cancer Res 61:2071–2079PubMedGoogle Scholar
  26. 26.
    Zhu J, Tseng YH, Kantor JD, Rhodes CJ, Zetter BR, Moyers JS, Kahn CR (1999) Interaction of the Ras-related protein associated with diabetes rad and the putative tumor metastasis suppressor NM23 provides a novel mechanism of GTPase regulation. Proc Natl Acad Sci USA 96:14911–14918. doi: 10.1073/pnas.96.26.14911 PubMedCrossRefGoogle Scholar
  27. 27.
    Otsuki Y, Tanaka M, Yoshii S, Kawazoe N, Nakaya K, Sugimura H (2001) Tumor metastasis suppressor nm23H1 regulates Rac1 GTPase by interaction with Tiam1. Proc Natl Acad Sci USA 98:4385–4390. doi: 10.1073/pnas.071411598 PubMedCrossRefGoogle Scholar
  28. 28.
    Hartsough MT, Morrison DK, Salerno M, Palmieri D, Ouatas T, Mair M, Patrick J, Steeg PS (2002) Nm23-H1 metastasis suppressor phosphorylation of kinase suppressor of Ras via a histidine protein kinase pathway. J Biol Chem 277:32389–32399. doi: 10.1074/jbc.M203115200 PubMedCrossRefGoogle Scholar
  29. 29.
    Iwashita S, Fujii M, Mukai H, Ono Y, Miyamoto M (2004) Lbc proto-oncogene product binds to and could be negatively regulated by metastasis suppressor nm23-H2. Biochem Biophys Res Commun 320:1063–1068. doi: 10.1016/j.bbrc.2004.06.067 PubMedCrossRefGoogle Scholar
  30. 30.
    Murakami M, Meneses PI, Knight JS, Lan K, Kaul R, Verma SC, Robertson ES (2008) Nm23-H1 modulates the activity of the guanine exchange factor Dbl-1. Int J Cancer 123:500–510. doi: 10.1002/ijc.23568 PubMedCrossRefGoogle Scholar
  31. 31.
    Baillat G, Gaillard S, Castets F, Monneron A (2002) Interactions of phocein with nucleoside-diphosphate kinase, Eps15, and Dynamin I. J Biol Chem 277:18961–18966. doi: 10.1074/jbc.M108818200 PubMedCrossRefGoogle Scholar
  32. 32.
    Gallagher BC, Parrott KA, Szabo G, de Otero S (2003) A receptor activation regulates cortical, but not vesicular localization of NDP kinase. J Cell Sci 116:3239–3250. doi: 10.1242/jcs.00630 PubMedCrossRefGoogle Scholar
  33. 33.
    Islam K, Burns RG (1985) Microtubules and nucleoside diphosphate kinase. Nucleoside diphosphate kinase binds to co-purifying contaminants rather than to microtubule proteins. Biochem J 232:651–656Google Scholar
  34. 34.
    Melki R, Lascu I, Carlier MF, Veron M (1992) Nucleoside diphosphate kinase does not directly interact with tubulin nor microtubules. Biochem Biophys Res Commun 187:65–72. doi: 10.1016/S0006-291X(05)81459-7 PubMedCrossRefGoogle Scholar
  35. 35.
    Duriez B, Duquesnoy P, Escudier E, Bridoux AM, Escalier D, Rayet I, Marcos E, Vojtek AM, Bercher JF, Amselem S (2007) A common variant in combination with a nonsense mutation in a member of the thioredoxin family causes primary ciliary dyskinesia. Proc Natl Acad Sci USA 104:3336–3341. doi: 10.1073/pnas.0611405104 PubMedCrossRefGoogle Scholar
  36. 36.
    Sadek CM, Jimenez A, Damdimopoulos AE, Kieselbach T, Nord M, Gustafsson JA, Spyrou G, Davis EC, Oko R, van der Hoorn FA, Miranda-Vizuete A (2003) Characterization of human thioredoxin-like 2. A novel microtubule-binding thioredoxin expressed predominantly in the cilia of lung airway epithelium and spermatid manchette and axoneme. J Biol Chem 278:13133–13142. doi: 10.1074/jbc.M300369200 PubMedCrossRefGoogle Scholar
  37. 37.
    Hippe HJ, Luedde M, Lutz S, Koehler H, Eschenhagen T, Frey N, Katus HA, Wieland T, Niroomand F (2007) Regulation of cardiac cAMP synthesis and contractility by nucleoside diphosphate kinase B/G protein beta gamma dimer complexes. Circ Res 100:1191–1199. doi: 10.1161/ PubMedCrossRefGoogle Scholar
  38. 38.
    Lutz S, Mura R, Baltus D, Movsesian M, Kubler W, Niroomand F (2001) Increased activity of membrane-associated nucleoside diphosphate kinase and inhibition of cAMP synthesis in failing human myocardium. Cardiovasc Res 49:48–55. doi: 10.1016/S0008-6363(00)00222-4 PubMedCrossRefGoogle Scholar
  39. 39.
    Lutz S, Hippe HJ, Niroomand F, Wieland T (2004) Nucleoside diphosphate kinase-mediated activation of heterotrimeric G proteins. Methods Enzymol 390:403–418. doi: 10.1016/S0076-6879(04)90025-0 PubMedCrossRefGoogle Scholar
  40. 40.
    Sheffler DJ, Kroeze WK, Garcia BG, Deutch AY, Hufeisen SJ, Leahy P, Bruning JC, Roth BL (2006) p90 ribosomal S6 kinase 2 exerts a tonic brake on G protein-coupled receptor signaling. Proc Natl Acad Sci USA 103:4717–4722. doi: 10.1073/pnas.0600585103 PubMedCrossRefGoogle Scholar
  41. 41.
    Kapetanovich L, Baughman C, Lee TH (2005) Nm23H2 facilitates coat protein complex II assembly and endoplasmic reticulum export in mammalian cells. Mol Biol Cell 16:835–848. doi: 10.1091/mbc.E04-09-0785 PubMedCrossRefGoogle Scholar
  42. 42.
    Alexander S, Srinivasan S, Alexander H (2003) Proteomics opens doors to the mechanisms of developmentally regulated secretion. Mol Cell Proteomics 2:1156–1163. doi: 10.1074/mcp.R300011-MCP200 PubMedCrossRefGoogle Scholar
  43. 43.
    Wallet V, Mutzel R, Troll H, Barzu O, Wurster B, Veron M, Lacombe ML (1990) Dictyostelium nucleoside diphosphate kinase highly homologous to Nm23 and Awd proteins involved in mammalian tumor metastasis and Drosophila development. J Natl Cancer Inst 82:1199–1202. doi: 10.1093/jnci/82.14.1199 PubMedCrossRefGoogle Scholar
  44. 44.
    Krishnan KS, Rikhy R, Rao S, Shivalkar M, Mosko M, Narayanan R, Etter P, Estes PS, Ramaswami M (2001) Nucleoside diphosphate kinase, a source of GTP, is required for dynamin-dependent synaptic vesicle recycling. Neuron 30:197–210. doi: 10.1016/S0896-6273(01)00273-2 PubMedCrossRefGoogle Scholar
  45. 45.
    Dammai V, Adryan B, Lavenburg KR, Hsu T (2003) Drosophila awd, the homolog of human nm23, regulates FGF receptor levels and functions synergistically with shi/dynamin during tracheal development. Genes Dev 17:2812–2824. doi: 10.1101/gad.1096903 PubMedCrossRefGoogle Scholar
  46. 46.
    Nallamothu G, Woolworth JA, Dammai V, Hsu T (2008) Awd, the homolog of metastasis suppressor gene Nm23, regulates Drosophila epithelial cell invasion. Mol Cell Biol 28:1964–1973. doi: 10.1128/MCB.01743-07 PubMedCrossRefGoogle Scholar
  47. 47.
    Palacios F, Schweitzer JK, Boshans RL, D’Souza-Schorey C (2002) ARF6-GTP recruits Nm23-H1 to facilitate dynamin-mediated endocytosis during adherens junctions disassembly. Nat Cell Biol 4:929–936. doi: 10.1038/ncb881 PubMedCrossRefGoogle Scholar
  48. 48.
    Horak CE, Lee JH, Elkahloun AG, Boissan M, Dumont S, Maga TK, Arnaud-Dabernat S, Palmieri D, Stetler-Stevenson WG, Lacombe ML, Meltzer PS, Steeg PS (2007) Nm23-H1 suppresses tumor cell motility by down-regulating the lysophosphatidic acid receptor EDG2. Cancer Res 67:7238–7246. doi: 10.1158/0008-5472.CAN-07-0962 PubMedCrossRefGoogle Scholar
  49. 49.
    Fournier HN, Albiges-Rizo C, Block MR (2003) New insights into Nm23 control of cell adhesion and migration. J Bioenerg Biomembr 35:81–87. doi: 10.1023/A:1023450008347 PubMedCrossRefGoogle Scholar
  50. 50.
    Ma D, McCorkle JR, Kaetzel DM (2004) The metastasis suppressor NM23-H1 possesses 3′-5′ exonuclease activity. J Biol Chem 279:18073–18084. doi: 10.1074/jbc.M400185200 PubMedCrossRefGoogle Scholar
  51. 51.
    Curtis CD, Likhite VS, McLeod IX, Yates JR, Nardulli AM (2007) Interaction of the tumor metastasis suppressor nonmetastatic protein 23 homologue H1 and estrogen receptor alpha alters estrogen-responsive gene expression. Cancer Res 67:10600–10607. doi: 10.1158/0008-5472.CAN-07-0055 PubMedCrossRefGoogle Scholar
  52. 52.
    Paravicini G, Steinmayr M, Andre E, Becker-Andre M (1996) The metastasis suppressor candidate nucleotide diphosphate kinase NM23 specifically interacts with members of the ROR/RZR nuclear orphan receptor subfamily. Biochem Biophys Res Commun 227:82–87. doi: 10.1006/bbrc.1996.1471 PubMedCrossRefGoogle Scholar
  53. 53.
    Rayner K, Chen YX, Hibbert B, White D, Miller H, Postel EH, O’Brien ER (2008) Discovery of NM23-H2 as an estrogen receptor beta-associated protein: role in estrogen-induced gene transcription and cell migration. J Steroid Biochem Mol Biol 108:72–81. doi: 10.1016/j.jsbmb.2007.07.006 PubMedCrossRefGoogle Scholar
  54. 54.
    Subramanian C, Cotter MAII, Robertson ES (2001) Epstein-Barr virus nuclear protein EBNA-3C interacts with the human metastatic suppressor Nm23-H1: a molecular link to cancer metastasis. Nat Med 7:350–355. doi: 10.1038/85499 PubMedCrossRefGoogle Scholar
  55. 55.
    Subramanian C, Robertson ES (2002) The metastatic suppressor Nm23-H1 interacts with EBNA3C at sequences located between the glutamine- and proline-rich domains and can cooperate in activation of transcription. J Virol 76:8702–8709. doi: 10.1128/JVI.76.17.8702-8709.2002 PubMedCrossRefGoogle Scholar
  56. 56.
    Kaul R, Murakami M, Choudhuri T, Robertson ES (2007) Epstein-Barr virus latent nuclear antigens can induce metastasis in a nude mouse model. J Virol 81:10352–10361. doi: 10.1128/JVI.00886-07 PubMedCrossRefGoogle Scholar
  57. 57.
    Mileo AM, Piombino E, Severino A, Tritarelli A, Paggi MG, Lombardi D (2006) Multiple interference of the human papillomavirus-16 E7 oncoprotein with the functional role of the metastasis suppressor Nm23-H1 protein. J Bioenerg Biomembr 38:215–225. doi: 10.1007/s10863-006-9037-y PubMedCrossRefGoogle Scholar
  58. 58.
    Seong HA, Jung H, Ha H (2007) NM23-H1 tumor suppressor physically interacts with serine-threonine kinase receptor-associated protein, a transforming growth factor-beta (TGF-beta) receptor-interacting protein, and negatively regulates TGF-beta signaling. J Biol Chem 282:12075–12096. doi: 10.1074/jbc.M609832200 PubMedCrossRefGoogle Scholar
  59. 59.
    Jung H, Seong HA, Ha H (2007) NM23-H1 tumor suppressor and its interacting partner STRAP activate p53 function. J Biol Chem 282:35293–35307. doi: 10.1074/jbc.M705181200 PubMedCrossRefGoogle Scholar
  60. 60.
    Jung H, Seong HA, Ha H (2008) Direct interaction between Nm23-H1 and macrophage amigration inhibitory factor (MIF) is critical for alleviation of MIF-mediated suppression of p53 activity. J Biol Chem 283:32669–32679Google Scholar
  61. 61.
    Kang Y, Lee DC, Han J, Yoon S, Won M, Yeom JH, Seong MJ, Ko JJ, Lee KA, Lee K, Bae J (2007) NM23-H2 involves in negative regulation of Diva and Bcl2L10 in apoptosis signaling. Biochem Biophys Res Commun 359:76–82. doi: 10.1016/j.bbrc.2007.05.090 PubMedCrossRefGoogle Scholar
  62. 62.
    Reymond A, Volorio S, Merla G, Al-Maghtheh M, Zuffardi O, Bulfone A, Ballabio A, Zollo M (1999) Evidence for interaction between human PRUNE and nm23-H1 NDPKinase. Oncogene 18:7244–7252. doi: 10.1038/sj.onc.1203140 PubMedCrossRefGoogle Scholar
  63. 63.
    D’Angelo A, Garzia L, Andre A, Carotenuto P, Aglio V, Guardiola O, Arrigoni G, Cossu A, Palmieri G, Aravind L, Zollo M (2004) Prune cAMP phosphodiesterase binds nm23-H1 and promotes cancer metastasis. Cancer Cell 5:137–149. doi: 10.1016/S1535-6108(04)00021-2 PubMedCrossRefGoogle Scholar
  64. 64.
    Srivastava S, Li Z, Ko K, Choudhury P, Albaqumi M, Johnson AK, Yan Y, Backer JM, Unutmaz D, Coetzee WA, Skolnik EY (2006) Histidine phosphorylation of the potassium channel KCa3.1 by nucleoside diphosphate kinase B is required for activation of KCa3.1 and CD4 T cells. Mol Cell 24:665–675. doi: 10.1016/j.molcel.2006.11.012 PubMedCrossRefGoogle Scholar
  65. 65.
    Srivastava S, Zhdanova O, Di L, Li Z, Albaqumi M, Wulff H, Skolnik EY (2008) Protein histidine phosphatase 1 negatively regulates CD4 T cells by inhibiting the K+ channel KCa3.1. Proc Natl Acad Sci USA 105:14442–14446. doi: 10.1073/pnas.0803678105 PubMedCrossRefGoogle Scholar
  66. 66.
    Schwahn U, Lenzner S, Dong J, Feil S, Hinzmann B, van Duijnhoven G, Kirschner R, Hemberger M, Bergen AA, Rosenberg T, Pinckers AJ, Fundele R, Rosenthal A, Cremers FP, Ropers HH, Berger W (1998) Positional cloning of the gene for X-linked retinitis pigmentosa 2. Nat Genet 19:327–332. doi: 10.1038/1214 PubMedCrossRefGoogle Scholar
  67. 67.
    Munier A, Serres C, Kann ML, Boissan M, Lesaffre C, Capeau J, Fouquet JP, Lacombe ML (2003) Nm23/NDP kinases in human male germ cells: role in spermiogenesis and sperm motility? Exp Cell Res 289:295–306. doi: 10.1016/S0014-4827(03)00268-4 PubMedCrossRefGoogle Scholar
  68. 68.
    Nagy PL, Griesenbeck J, Kornberg RD, Cleary ML (2002) A trithorax-group complex purified from Saccharomyces cerevisiae is required for methylation of histone H3. Proc Natl Acad Sci USA 99:90–94. doi: 10.1073/pnas.221596698 PubMedCrossRefGoogle Scholar
  69. 69.
    King SM (2006) Axonemal protofilament ribbons, DM10 domains, and the link to juvenile myoclonic epilepsy. Cell Motil Cytoskeleton 63:245–253. doi: 10.1002/cm.20129 PubMedCrossRefGoogle Scholar
  70. 70.
    Miranda-Vizuete A, Sadek CM, Jimenez A, Krause WJ, Sutovsky P, Oko R (2004) The mammalian testis-specific thioredoxin system. Antioxid Redox Signal 6:25–40. doi: 10.1089/152308604771978327 PubMedCrossRefGoogle Scholar
  71. 71.
    Ogawa K, Takai H, Ogiwara A, Yokota E, Shimizu T, Inaba K, Mohri H (1996) Is outer arm dynein intermediate chain 1 multifunctional? Mol Biol Cell 7:1895–1907PubMedGoogle Scholar
  72. 72.
    Padma P, Hozumi A, Ogawa K, Inaba K (2001) Molecular cloning and characterization of a thioredoxin/nucleoside diphosphate kinase related dynein intermediate chain from the ascidian, Ciona intestinalis. Gene 275:177–183. doi: 10.1016/S0378-1119(01)00661-8 PubMedCrossRefGoogle Scholar
  73. 73.
    Miranda-Vizuete A, Tsang K, Yu Y, Jimenez A, Pelto-Huikko M, Flickinger CJ, Sutovsky P, Oko R (2003) Cloning and developmental analysis of murid spermatid-specific thioredoxin-2 (SPTRX-2), a novel sperm fibrous sheath protein and autoantigen. J Biol Chem 278:44874–44885. doi: 10.1074/jbc.M305475200 PubMedCrossRefGoogle Scholar
  74. 74.
    Mahr S, Burmester GR, Hilke D, Gobel U, Grutzkau A, Haupl T, Hauschild M, Koczan D, Krenn V, Neidel J, Perka C, Radbruch A, Thiesen HJ, Muller B (2006) Cis- and trans-acting gene regulation is associated with osteoarthritis. Am J Hum Genet 78:793–803. doi: 10.1086/503849 PubMedCrossRefGoogle Scholar
  75. 75.
    Tian G, Bhamidipati A, Cowan NJ, Lewis SA (1999) Tubulin folding cofactors as GTPase-activating proteins, GTP hydrolysis and the assembly of the alpha/beta-tubulin heterodimer. J Biol Chem 274:24054–24058. doi: 10.1074/jbc.274.34.24054 PubMedCrossRefGoogle Scholar
  76. 76.
    Veltel S, Gasper R, Eisenacher E, Wittinghofer A (2008) The retinitis pigmentosa 2 gene product is a GTPase-activating protein for Arf-like 3. Nat Struct Mol Biol 15:373–380. doi: 10.1038/nsmb.1396 PubMedCrossRefGoogle Scholar
  77. 77.
    Yoon JH, Singh P, Lee DH, Qiu J, Cai S, O’Connor TR, Chen Y, Shen B, Pfeifer GP (2005) Characterization of the 3′ --> 5′ exonuclease activity found in human nucleoside diphosphate kinase 1 (NDK1) and several of its homologues. Biochemistry 44:15774–15786. doi: 10.1021/bi0515974 PubMedCrossRefGoogle Scholar
  78. 78.
    Yoon JH, Qiu J, Cai S, Chen Y, Cheetham ME, Shen B, Pfeifer GP (2006) The retinitis pigmentosa-mutated RP2 protein exhibits exonuclease activity and translocates to the nucleus in response to DNA damage. Exp Cell Res 312:1323–1334. doi: 10.1016/j.yexcr.2005.12.026 PubMedCrossRefGoogle Scholar
  79. 79.
    Mitchell KA, Gallagher BC, Szabo G, Otero Ade S (2004) NDP kinase moves into developing primary cilia. Cell Motil Cytoskeleton 59:62–73. doi: 10.1002/cm.20025 PubMedCrossRefGoogle Scholar
  80. 80.
    Scholey JM (2008) Intraflagellar transport motors in cilia: moving along the cell’s antenna. J Cell Biol 180:23–29. doi: 10.1083/jcb.200709133 PubMedCrossRefGoogle Scholar
  81. 81.
    Herbert E, Potter VR, Takagi Y (1955) The phosphorylation of 5′-uridine nucleotides by cell fractions from rat liver. J Biol Chem 213:923–939PubMedGoogle Scholar
  82. 82.
    Brdiczka D, Beutner G, Ruck A, Dolder M, Wallimann T (1998) The molecular structure of mitochondrial contact sites, their role in regulation of energy metabolism and permeability transition. Biofactors 8:235–242. doi: 10.1002/biof.5520080311 PubMedCrossRefGoogle Scholar
  83. 83.
    Muhonen WW, Lambeth DO (1995) The compartmentation of nucleoside diphosphate kinase in mitochondria. Comp Biochem Physiol B Biochem Mol Biol 110:211–223. doi: 10.1016/0305-0491(94)00123-C PubMedCrossRefGoogle Scholar
  84. 84.
    Krebs HA, Wiggins D (1978) Phosphorylation of adenosine monophosphate in the mitochondrial matrix. Biochem J 174:297–301PubMedGoogle Scholar
  85. 85.
    Gordon DM, Lyver ER, Lesuisse E, Dancis A, Pain D (2006) GTP in the mitochondrial matrix plays a crucial role in organellar iron homoeostasis. Biochem J 400:163–168. doi: 10.1042/BJ20060904 PubMedCrossRefGoogle Scholar
  86. 86.
    Pedersen PL (1973) Coupling of adenosine triphosphate formation in mitochondria to the formation of nucleoside triphosphates. Involvement of nucleoside diphosphokinase. J Biol Chem 248:3956–3962PubMedGoogle Scholar
  87. 87.
    Milon L, Rousseau-Merck MF, Munier A, Erent M, Lascu I, Capeau J, Lacombe ML (1997) nm230-H4, a new member of the family of human nm23/nucleoside diphosphate kinase genes localised on chromosome 16p13. Hum Genet 99:550–557. doi: 10.1007/s004390050405 PubMedCrossRefGoogle Scholar
  88. 88.
    Barraud P, Amrein L, Dobremez E, Dabernat S, Masse K, Larou M, Daniel JY, Landry M (2002) Differential expression of nm23 genes in adult mouse dorsal root ganglia. J Comp Neurol 444:306–323. doi: 10.1002/cne.10150 PubMedCrossRefGoogle Scholar
  89. 89.
    Knorpp C, Johansson M, Baird AM (2003) Plant mitochondrial nucleoside diphosphate kinase is attached to the membrane through interaction with the adenine nucleotide translocator. FEBS Lett 555:363–366. doi: 10.1016/S0014-5793(03)01288-2 PubMedCrossRefGoogle Scholar
  90. 90.
    Epand RF, Tokarska-Schlattner M, Schlattner U, Wallimann T, Epand RM (2007) Cardiolipin clusters and membrane domain formation induced by mitochondrial proteins. J Mol Biol 365:968–980. doi: 10.1016/j.jmb.2006.10.028 PubMedCrossRefGoogle Scholar
  91. 91.
    Janin J, Dumas C, Morera S, Xu Y, Meyer P, Chiadmi M, Cherfils J (2000) Three-dimensional structure of nucleoside diphosphate kinase. J Bioenerg Biomembr 32:215–225. doi: 10.1023/A:1005528811303 PubMedCrossRefGoogle Scholar
  92. 92.
    Min K, Song HK, Chang C, Kim SY, Lee KJ, Suh SW (2002) Crystal structure of human nucleoside diphosphate kinase A, a metastasis suppressor. Proteins 46:340–342. doi: 10.1002/prot.10038 PubMedCrossRefGoogle Scholar
  93. 93.
    Chen Y, Gallois-Montbrun S, Schneider B, Veron M, Morera S, Deville-Bonne D, Janin J (2003) Nucleotide binding to nucleoside diphosphate kinases: X-ray structure of human NDPK-A in complex with ADP and comparison to protein kinases. J Mol Biol 332:915–926. doi: 10.1016/j.jmb.2003.07.004 PubMedCrossRefGoogle Scholar
  94. 94.
    Giraud MF, Georgescauld F, Lascu I, Dautant A (2006) Crystal structures of S120G mutant and wild type of human nucleoside diphosphate kinase A in complex with ADP. J Bioenerg Biomembr 38:261–264. doi: 10.1007/s10863-006-9043-0 PubMedCrossRefGoogle Scholar
  95. 95.
    Chang CL, Zhu XX, Thoraval DH, Ungar D, Rawwas J, Hora N, Strahler JR, Hanash SM, Radany E (1994) Nm23-H1 mutation in neuroblastoma. Nature 370:335–336. doi: 10.1038/370335a0 PubMedCrossRefGoogle Scholar
  96. 96.
    Erent M, Gonin P, Cherfils J, Tissier P, Raschella G, Giartosio A, Agou F, Sarger C, Lacombe ML, Konrad M, Lascu I (2001) Structural and catalytic properties and homology modelling of the human nucleoside diphosphate kinase C, product of the DRnm23 gene. Eur J Biochem 268:1972–1981. doi: 10.1046/j.1432-1327.2001.2076.doc.x PubMedCrossRefGoogle Scholar
  97. 97.
    Morera S, Lacombe ML, Xu Y, LeBras G, Janin J (1995) X-ray structure of human nucleoside diphosphate kinase B complexed with GDP at 2 A resolution. Structure 3:1307–1314. doi: 10.1016/S0969-2126(01)00268-4 PubMedCrossRefGoogle Scholar
  98. 98.
    Lascu I, Schaertl S, Wang C, Sarger C, Giartosio A, Briand G, Lacombe ML, Konrad M (1997) A point mutation of human nucleoside diphosphate kinase A found in aggressive neuroblastoma affects protein folding. J Biol Chem 272:15599–15602. doi: 10.1074/jbc.272.25.15599 PubMedCrossRefGoogle Scholar
  99. 99.
    Lascu I, Giartosio A, Ransac S, Erent M (2000) Quaternary structure of nucleoside diphosphate kinases. J Bioenerg Biomembr 32:227–236. doi: 10.1023/A:1005580828141 PubMedCrossRefGoogle Scholar
  100. 100.
    Zhou Q, Yang X, Zhu D, Ma L, Zhu W, Sun Z, Yang Q (2007) Double mutant P96S/S120G of Nm23-H1 abrogates its NDPK activity and motility-suppressive ability. Biochem Biophys Res Commun 356:348–353. doi: 10.1016/j.bbrc.2007.02.066 PubMedCrossRefGoogle Scholar
  101. 101.
    Lascu I, Chaffotte A, Limbourg-Bouchon B, Veron M (1992) A Pro/Ser substitution in nucleoside diphosphate kinase of Drosophila melanogaster (mutation killer of prune) affects stability but not catalytic efficiency of the enzyme. J Biol Chem 267:12775–12781PubMedGoogle Scholar
  102. 102.
    Mocan I, Georgescauld F, Gonin P, Thoraval D, Cervoni L, Giartosio A, Dabernat-Arnaud S, Crouzet M, Lacombe ML, Lascu I (2007) Protein phosphorylation corrects the folding defect of the neuroblastoma (S120G) mutant of human nucleoside diphosphate kinase A/Nm23-H1. Biochem J 403:149–156. doi: 10.1042/BJ20061141 PubMedCrossRefGoogle Scholar
  103. 103.
    Dabernat S, Larou M, Masse K, Dobremez E, Landry M, Mathieu C, Daniel JY (1999) Organization and expression of mouse nm23-M1 gene. Comparison with nm23-M2 expression. Gene 236:221–230. doi: 10.1016/S0378-1119(99)00288-7 PubMedCrossRefGoogle Scholar
  104. 104.
    Arnaud-Dabernat S, Bourbon PM, Dierich A, Le Meur M, Daniel JY (2003) Knockout mice as model systems for studying nm23/NDP kinase gene functions. Application to the nm23-M1 gene. J Bioenerg Biomembr 35:19–30. doi: 10.1023/A:1023561821551 PubMedCrossRefGoogle Scholar
  105. 105.
    Boissan M, Wendum D, Arnaud-Dabernat S, Munier A, Debray M, Lascu I, Daniel JY, Lacombe ML (2005) Increased lung metastasis in transgenic NM23-Null/SV40 mice with hepatocellular carcinoma. J Natl Cancer Inst 97:836–845PubMedCrossRefGoogle Scholar
  106. 106.
    Masse K, Dabernat S, Bourbon PM, Larou M, Amrein L, Barraud P, Perel Y, Camara M, Landry M, Lacombe ML, Daniel JY (2002) Characterization of the nm23-M2, nm23-M3 and nm23-M4 mouse genes: comparison with their human orthologs. Gene 296:87–97. doi: 10.1016/S0378-1119(02)00836-3 PubMedCrossRefGoogle Scholar
  107. 107.
    Dzeja PP, Terzic A (2003) Phosphotransfer networks and cellular energetics. J Exp Biol 206:2039–2047. doi: 10.1242/jeb.00426 PubMedCrossRefGoogle Scholar
  108. 108.
    Morin-Leisk J, Lee TH (2008) Nucleotide-dependent self-assembly of nucleoside diphosphate kinase (NDPK) in vitro. Biochim Biophys Acta 1784:2045–2051Google Scholar
  109. 109.
    Baughman C, Morin-Leisk J, Lee T (2008) Nucleoside diphosphate kinase B (NDKB) scaffolds endoplasmic reticulum membranes in vitro. Exp Cell Res 314:2702–2714. doi: 10.1016/j.yexcr.2008.06.005 PubMedCrossRefGoogle Scholar
  110. 110.
    Mitchell KA, Szabo G, de S Otero A (2009) Direct binding of cytosolic NDP kinases to membrane lipids is regulated by nucleotides. Biochim Biophys Acta 1793:469–476. doi: 10.1016/j.bbamcr.2008.12.009 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Mathieu Boissan
    • 1
  • Sandrine Dabernat
    • 2
  • Evelyne Peuchant
    • 2
  • Uwe Schlattner
    • 3
  • Ioan Lascu
    • 4
  • Marie-Lise Lacombe
    • 1
    Email author
  1. 1.INSERM UMRS_938, UMPC Université Paris 06ParisFrance
  2. 2.INSERM U876, Université de Bordeaux-2BordeauxFrance
  3. 3.INSERM U884, Université Joseph FourierGrenobleFrance
  4. 4.Institut de Biochimie et Génétique CellulairesCNRS UMR 5095, Université de Bordeaux-2BordeauxFrance

Personalised recommendations