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Gene Review

NME1  -  NME/NM23 nucleoside diphosphate kinase 1

Homo sapiens

Synonyms: AWD, GAAD, Granzyme A-activated DNase, Metastasis inhibition factor nm23, NB, ...
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Disease relevance of NME1


High impact information on NME1


Chemical compound and disease context of NME1


Biological context of NME1


Anatomical context of NME1

  • NDP kinase A was transiently located in round spermatid nuclei and became asymmetrically distributed in the cytoplasm at the nuclear basal pole of elongating spermatids [17].
  • It also was reported that extracellular NM23 could inhibit differentiation of certain hematopoietic cell lines [18].
  • MATERIALS AND METHODS: To study the effect on the earlier stages of hematopoietic maturation, NM23 was added to serum-free pre-colony-forming unit (pre-CFU) assays starting from immature CD34++CD38- bone marrow cells [18].
  • In contrast, terminal differentiation of CD34+CD38+ progenitor cells in CFU assays was significantly altered by addition of NM23 protein [18].
  • More erythroid burst-forming units and fewer macrophage colonies were observed in cultures containing any of the NM23 isoforms examined [18].

Associations of NME1 with chemical compounds


Physical interactions of NME1

  • The centrosomal kinase Aurora-A/STK15 interacts with a putative tumor suppressor NM23-H1 [22].
  • Moreover, both NM23-H1 and Nm23-H2 bind to nuclease hypersensitive elements in the platelet-derived growth factor PDGF-A gene promoter sequence-specifically, correlating with either positive or negative transcriptional regulation [23].
  • Furthermore, the nm23-H1 (-)/E-cadherin (+) coexpression profile was coupled to decreased E-cadherin immunohistochemical protein detection (grade II) in 21% of the cases examined [24].
  • The exonuclease TREX1 is in the SET complex and acts in concert with NM23-H1 to degrade DNA during granzyme A-mediated cell death [25].

Regulatory relationships of NME1


Other interactions of NME1

  • Subsequently, two related human nm23 genes, nm23-H1 and nm23-H2, were identified [32].
  • Of the 4 loci tested, LOH at TP53, D17S74, and NME1 was associated with clinical stage [3].
  • P-glycoprotein, metallothionein and NM23 protein expressions in breast carcinoma [33].
  • The higher level of NM23-H1 was correlated with a worse outcome in patients with a single MYCN copy, or in those younger than 12 months of age [34].
  • STK15 and NM23 were initially found to interact in yeast in a two-hybrid assay [22].

Analytical, diagnostic and therapeutic context of NME1


  1. Identification of three regions on chromosome 17q in primary human breast carcinomas which are frequently deleted. Cropp, C.S., Champeme, M.H., Lidereau, R., Callahan, R. Cancer Res. (1993) [Pubmed]
  2. Localization of a second NM23 gene, NME2, to chromosome 17q21-q22. Kelsell, D.P., Black, D.M., Solomon, E., Spurr, N.K. Genomics (1993) [Pubmed]
  3. Genetic alterations on chromosome 17 in human breast cancer: relationships to clinical features and DNA ploidy. Watatani, M., Nagayama, K., Imanishi, Y., Kurooka, K., Wada, T., Inui, H., Hirai, K., Ozaki, M., Yasutomi, M. Breast Cancer Res. Treat. (1993) [Pubmed]
  4. Differential expression and mutation of NME genes in autologous cultured human melanoma cells with different metastatic potentials. Hamby, C.V., Mendola, C.E., Potla, L., Stafford, G., Backer, J.M. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  5. Frequent loss of heterozygosity for Rb, TP53, and chromosome arm 3p, but not NME1 in squamous cell carcinomas of the supraglottic larynx. Scholnick, S.B., Sun, P.C., Shaw, M.E., Haughey, B.H., el-Mofty, S.K. Cancer (1994) [Pubmed]
  6. Tumor suppressor NM23-H1 is a granzyme A-activated DNase during CTL-mediated apoptosis, and the nucleosome assembly protein SET is its inhibitor. Fan, Z., Beresford, P.J., Oh, D.Y., Zhang, D., Lieberman, J. Cell (2003) [Pubmed]
  7. Drosophila awdK-pn, a homologue of the metastasis suppressor gene nm23, suppresses the Tum-1 haematopoietic oncogene. Zinyk, D.L., McGonnigal, B.G., Dearolf, C.R. Nat. Genet. (1993) [Pubmed]
  8. Granzyme A induces caspase-independent mitochondrial damage, a required first step for apoptosis. Martinvalet, D., Zhu, P., Lieberman, J. Immunity (2005) [Pubmed]
  9. Cell cycle effects and control of gene expression by resveratrol in human breast carcinoma cell lines with different metastatic potentials. Hsieh, T.C., Burfeind, P., Laud, K., Backer, J.M., Traganos, F., Darzynkiewicz, Z., Wu, J.M. Int. J. Oncol. (1999) [Pubmed]
  10. NM23 gene expression in human prostatic carcinomas and benign prostatic hyperplasias: altered expression in combined androgen blockaded carcinomas. Borchers, H., Meyers, F.J., Gumerlock, P.H., Stewart, S.L., deVere White, R.W. J. Urol. (1996) [Pubmed]
  11. Expression of nm23-H1 gene product in sarcomatous cancer cells of renal cell carcinoma: correlation with tumor stage and expression of matrix metalloproteinase-2, matrix metalloproteinase-9, sialyl Lewis X, and c-erbB-2. Ohba, K., Miyata, Y., Koga, S., Kanda, S., Kanetake, H. Urology (2005) [Pubmed]
  12. Suppression of human melanoma metastasis following introduction of chromosome 6 is independent of NME1 (Nm23). Miele, M.E., De La Rosa, A., Lee, J.H., Hicks, D.J., Dennis, J.U., Steeg, P.S., Welch, D.R. Clin. Exp. Metastasis (1997) [Pubmed]
  13. Immunohistochemical evaluation of nm23-H1 gene product in transitional cell carcinoma of the bladder. Nakopoulou, L.L., Constandinides, C.A., Tzonou, A., Lazaris, A.C., Zervas, A., Dimopoulos, C.A. Histopathology (1996) [Pubmed]
  14. The human NME2 gene lies within 18kb of NME1 in chromosome 17. Chandrasekharappa, S.C., Gross, L.A., King, S.E., Collins, F.S. Genes Chromosomes Cancer (1993) [Pubmed]
  15. Increased expression of the NME1 gene is associated with metastasis in epithelial ovarian cancer. Leary, J.A., Kerr, J., Chenevix-Trench, G., Doris, C.P., Hurst, T., Houghton, C.R., Friedlander, M.L. Int. J. Cancer (1995) [Pubmed]
  16. Genomic instability is associated with lack of telomerase activation in ovarian cancer. Landen, C.N., Klingelhutz, A., Coffin, J.E., Sorosky, J.I., Sood, A.K. Cancer Biol. Ther. (2004) [Pubmed]
  17. Nm23/NDP kinases in human male germ cells: role in spermiogenesis and sperm motility? Munier, A., Serres, C., Kann, M.L., Boissan, M., Lesaffre, C., Capeau, J., Fouquet, J.P., Lacombe, M.L. Exp. Cell Res. (2003) [Pubmed]
  18. Extracellular nucleoside diphosphate kinase NM23/NDPK modulates normal hematopoietic differentiation. Willems, R., Slegers, H., Rodrigus, I., Moulijn, A.C., Lenjou, M., Nijs, G., Berneman, Z.N., Van Bockstaele, D.R. Exp. Hematol. (2002) [Pubmed]
  19. Transfection of the nm23-H1 gene into human hepatocarcinoma cell line inhibits the expression of sialyl Lewis X, alpha1,3 fucosyltransferase VII, and metastatic potential. Liu, F., Zhang, Y., Zhang, X.Y., Chen, H.L. J. Cancer Res. Clin. Oncol. (2002) [Pubmed]
  20. Site-directed mutagenesis of nm23-H1. Mutation of proline 96 or serine 120 abrogates its motility inhibitory activity upon transfection into human breast carcinoma cells. MacDonald, N.J., Freije, J.M., Stracke, M.L., Manrow, R.E., Steeg, P.S. J. Biol. Chem. (1996) [Pubmed]
  21. The nucleoside diphosphate kinase of human neutrophils. Guignard, F., Markert, M. Biochem. J. (1996) [Pubmed]
  22. The centrosomal kinase Aurora-A/STK15 interacts with a putative tumor suppressor NM23-H1. Du, J., Hannon, G.J. Nucleic Acids Res. (2002) [Pubmed]
  23. Human NM23/nucleoside diphosphate kinase regulates gene expression through DNA binding to nuclease-hypersensitive transcriptional elements. Postel, E.H., Berberich, S.J., Rooney, J.W., Kaetzel, D.M. J. Bioenerg. Biomembr. (2000) [Pubmed]
  24. High frequency of concomitant nm23-H1 and E-cadherin transcriptional inactivation in primary non-inheriting colorectal carcinomas. Garinis, G.A., Manolis, E.N., Spanakis, N.E., Patrinos, G.P., Peros, G., Menounos, P.G. J. Mol. Med. (2003) [Pubmed]
  25. The exonuclease TREX1 is in the SET complex and acts in concert with NM23-H1 to degrade DNA during granzyme A-mediated cell death. Chowdhury, D., Beresford, P.J., Zhu, P., Zhang, D., Sung, J.S., Demple, B., Perrino, F.W., Lieberman, J. Mol. Cell (2006) [Pubmed]
  26. Protein expression profiles indicative for drug resistance of non-small cell lung cancer. Volm, M., Koomägi, R., Mattern, J., Efferth, T. Br. J. Cancer (2002) [Pubmed]
  27. A novel physical and functional association between nucleoside diphosphate kinase A and AMP-activated protein kinase alpha1 in liver and lung. Crawford, R.M., Treharne, K.J., Best, O.G., Muimo, R., Riemen, C.E., Mehta, A. Biochem. J. (2005) [Pubmed]
  28. Tumor metastasis suppressor nm23H1 regulates Rac1 GTPase by interaction with Tiam1. Otsuki, Y., Tanaka, M., Yoshii, S., Kawazoe, N., Nakaya, K., Sugimura, H. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  29. NM23-H1 and NM23-H2 repress transcriptional activities of nuclease-hypersensitive elements in the platelet-derived growth factor-A promoter. Ma, D., Xing, Z., Liu, B., Pedigo, N.G., Zimmer, S.G., Bai, Z., Postel, E.H., Kaetzel, D.M. J. Biol. Chem. (2002) [Pubmed]
  30. Inhibitory action of nm23 proteins on induction of erythroid differentiation of human leukemia cells. Okabe-Kado, J., Kasukabe, T., Baba, H., Urano, T., Shiku, H., Honma, Y. Biochim. Biophys. Acta (1995) [Pubmed]
  31. 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. Seong, H.A., Jung, H., Ha, H. J. Biol. Chem. (2007) [Pubmed]
  32. NM23-H1 and NM23-H2 messenger RNA abundance in human hepatocellular carcinoma. Iizuka, N., Oka, M., Noma, T., Nakazawa, A., Hirose, K., Suzuki, T. Cancer Res. (1995) [Pubmed]
  33. P-glycoprotein, metallothionein and NM23 protein expressions in breast carcinoma. Vázquez-Ramírez, F.J., González-Cámpora, J.J., Hevia-Alvarez, E., Fernández-Santos, J.M., Ríos-Martín, J.J., Otal-Salaverri, C., González-Cámpora, R. Pathol. Res. Pract. (2000) [Pubmed]
  34. Clinical significance of serum NM23-H1 protein in neuroblastoma. Okabe-Kado, J., Kasukabe, T., Honma, Y., Hanada, R., Nakagawara, A., Kaneko, Y. Cancer Sci. (2005) [Pubmed]
  35. DNA ploidy and S-phase fraction, but not p53 or NM23-H1 expression, predict outcome in colorectal cancer patients. Result of a 5-year prospective study. Bazan, V., Migliavacca, M., Zanna, I., Tubiolo, C., Corsale, S., Calò, V., Amato, A., Cammareri, P., Latteri, F., Grassi, N., Fulfaro, F., Porcasi, R., Morello, V., Nuara, R.B., Dardanoni, G., Salerno, S., Valerio, M.R., Dusonchet, L., Gerbino, A., Gebbia, N., Tomasino, R.M., Russo, A. J. Cancer Res. Clin. Oncol. (2002) [Pubmed]
  36. NM23-H1 and NM23-H2 gene expression in human renal tumors. Theisinger, B., Engel, M., Seifert, M., Seitz, G., Welter, C. Anticancer Res. (1998) [Pubmed]
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