Skip to main content

Advertisement

SpringerLink
Log in

Regulators affecting the metastasis suppressor activity of Nm23-H1

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Nm23-H1 encodes nucleoside diphosphate kinase A (NDPK-A) and is known to have a metastasis suppressive activity in many tumor cells. However, it has many other functions as well. Recent studies have shown that the interacting proteins with Nm23-H1 which mediate the cell proliferation, may act as modulators of the metastasis suppressor activity. The interacting proteins with Nm23-H1 can be classified into 3 groups. The first group of proteins can be classified as upstream kinases of Nm23-H1 such as CKI and Aurora-A/STK15. The second group of proteins acts as downstream effectors for the regulation of specific gene transcriptions, GTP-binding protein functions, and signal transduction in Erk signal cascade. The third group of proteins can be classified as bi-directionally influencing binding partners of Nm23-H1. As a result, the interactions with Nm23-H1 and binding partners have implications in the biochemical characterization involved in metastasis and tumorigenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hartsough MT, Steeg PS (2000) Nm23/nucleoside diphosphate kinase in human cancers. J Bioenerg Biomembr 32:301–308. doi:10.1023/A:1005597231776

    Article  PubMed  CAS  Google Scholar 

  2. Okabe-Kado J, Kasukabe T (2003) Physiological and pathological relevance of extracellular NM23/NDP kinases. J Bioenerg Biomembr 35:89–93. doi:10.1023/A:1023402125186

    Article  PubMed  CAS  Google Scholar 

  3. Willems R, Slegers H, Rodrigus I, Moulijn AC, Lenjou M, Nijs G, Berneman ZN, Van Bockstaele DR (2002) Extracellular nucleoside diphosphate kinase NM23/NDPK modulates normal hematopoietic differentiation. Exp Hematol 30:640–648. doi:10.1016/S0301-472X(02)00809-3

    Article  PubMed  CAS  Google Scholar 

  4. Rumjahn SM, Javed MA, Wong N, Law WE, Buxton IL (2007) Purinergic regulation of angiogenesis by human breast carcinoma-secreted nucleoside diphosphate kinase. Br J Cancer 97:1372–1380. doi:10.1038/sj.bjc.6604019

    Article  PubMed  CAS  Google Scholar 

  5. Buckley KA, Golding SL, Rice JM, Dillon JP, Gallagher JA (2003) Release and interconversion of P2 receptor agonists by human osteoblast-like cells. FASEB J 17:1401–1410. doi:10.1096/fj.02-0940com

    Article  PubMed  CAS  Google Scholar 

  6. Wagner PD, Vu ND (2000) Histidine to aspartate phosphotransferase activity of nm23 proteins: phosphorylation of aldolase C on Asp-319. Biochem J 346(Pt 3):623–630. doi:10.1042/0264-6021:3460623

    Article  PubMed  CAS  Google Scholar 

  7. 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

    Article  PubMed  CAS  Google Scholar 

  8. 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

    Article  PubMed  CAS  Google Scholar 

  9. Chowdhury D, Beresford PJ, Zhu P, Zhang D, Sung JS, Demple B, Perrino FW, Lieberman J (2006) The exonuclease TREX1 is in the SET complex and acts in concert with NM23-H1 to degrade DNA during granzyme A-mediated cell death. Mol Cell 23:133–142. doi:10.1016/j.molcel.2006.06.005

    Article  PubMed  CAS  Google Scholar 

  10. 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

    Article  PubMed  CAS  Google Scholar 

  11. Garzia L, D’Angelo A, Amoresano A, Knauer SK, Cirulli C, Campanella C, Stauber RH, Steegborn C, Iolascon A, Zollo M (2008) Phosphorylation of nm23-H1 by CKI induces its complex formation with h-prune and promotes cell motility. Oncogene 27:1853–1864. doi:10.1038/sj.onc.1210822

    Article  PubMed  CAS  Google Scholar 

  12. Du J, Hannon GJ (2002) The centrosomal kinase Aurora-A/STK15 interacts with a putative tumor suppressor NM23-H1. Nucleic Acids Res 30:5465–5475. doi:10.1093/nar/gkf678

    Article  PubMed  CAS  Google Scholar 

  13. Kaul R, Murakami M, Lan K, Choudhuri T, Robertson ES (2009) EBNA3C can modulate the activities of the transcription factor Necdin in association with the metastasis suppressor protein Nm23-H1. J Virol. doi:10.1128/JVI.02286-08

    PubMed  Google Scholar 

  14. Murakami M, Lan K, Subramanian C, Robertson ES (2005) Epstein-Barr virus nuclear antigen 1 interacts with Nm23-H1 in lymphoblastoid cell lines and inhibits its ability to suppress cell migration. J Virol 79:1559–1568. doi:10.1128/JVI.79.3.1559-1568.2005

    Article  PubMed  CAS  Google Scholar 

  15. Choudhuri T, Verma SC, Lan K, Robertson ES (2006) Expression of alpha V integrin is modulated by Epstein-Barr virus nuclear antigen 3C and the metastasis suppressor Nm23-H1 through interaction with the GATA-1 and Sp1 transcription factors. Virology 351:58–72. doi:10.1016/j.virol.2006.03.031

    Article  PubMed  CAS  Google Scholar 

  16. 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

    Article  PubMed  CAS  Google Scholar 

  17. Fuqua SA (2001) The role of estrogen receptors in breast cancer metastasis. J Mammary Gland Biol Neoplasia 6:407–417. doi:10.1023/A:1014782813943

    Article  PubMed  CAS  Google Scholar 

  18. Lin KH, Wang WJ, Wu YH, Cheng SY (2002) Activation of antimetastatic Nm23–H1 gene expression by estrogen and its alpha-receptor. Endocrinology 143:467–475. doi:10.1210/en.143.2.467

    Article  PubMed  CAS  Google Scholar 

  19. Youn B, Kim HD, Kim J (2008) Nm23-H1/nucleoside diphosphate kinase as a key molecule in breast tumor angiogenesis. Expert Opin Ther Targets 12:1419–1430. doi:10.1517/14728222.12.11.1419

    Article  PubMed  CAS  Google Scholar 

  20. 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

    Article  PubMed  CAS  Google Scholar 

  21. 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

    Article  PubMed  CAS  Google Scholar 

  22. 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

    Article  PubMed  CAS  Google Scholar 

  23. 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 61:2071–2079

    PubMed  CAS  Google Scholar 

  24. 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

    Article  PubMed  CAS  Google Scholar 

  25. Zollo M, Andre A, Cossu A, Sini MC, D’Angelo A, Marino N, Budroni M, Tanda F, Arrigoni G, Palmieri G (2005) Overexpression of h-prune in breast cancer is correlated with advanced disease status. Clin Cancer Res 11:199–205

    PubMed  CAS  Google Scholar 

  26. Forus A, D’Angelo A, Henriksen J, Merla G, Maelandsmo GM, Florenes VA, Olivieri S, Bjerkehagen B, Meza-Zepeda LA, del Vecchio Blanco F, Muller C, Sanvito F, Kononen J, Nesland JM, Fodstad O, Reymond A, Kallioniemi OP, Arrigoni G, Ballabio A, Myklebost O, Zollo M (2001) Amplification and overexpression of PRUNE in human sarcomas and breast carcinomas-a possible mechanism for altering the nm23-H1 activity. Oncogene 20:6881–6890. doi:10.1038/sj.onc.1204874

    Article  PubMed  CAS  Google Scholar 

  27. 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

    Article  PubMed  CAS  Google Scholar 

  28. Garzia L, Roma C, Tata N, Pagnozzi D, Pucci P, Zollo M (2006) H-prune-nm23-H1 protein complex and correlation to pathways in cancer metastasis. J Bioenerg Biomembr 38:205–213. doi:10.1007/s10863-006-9036-z

    Article  PubMed  CAS  Google Scholar 

  29. 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

    Article  PubMed  Google Scholar 

  30. 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

    Article  PubMed  CAS  Google Scholar 

  31. 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

    Article  PubMed  CAS  Google Scholar 

  32. Wan F, Anderson DE, Barnitz RA, Snow A, Bidere N, Zheng L, Hegde V, Lam LT, Staudt LM, Levens D, Deutsch WA, Lenardo MJ (2007) Ribosomal protein S3: a KH domain subunit in NF-kappaB complexes that mediates selective gene regulation. Cell 131:927–939. doi:10.1016/j.cell.2007.10.009

    Article  PubMed  CAS  Google Scholar 

  33. Kim TS, Jang CY, Kim HD, Lee JY, Ahn BY, Kim J (2006) Interaction of Hsp90 with ribosomal proteins protects from ubiquitination and proteasome-dependent degradation. Mol Biol Cell 17:824–833. doi:10.1091/mbc.E05-08-0713

    Article  PubMed  CAS  Google Scholar 

  34. Jang CY, Lee JY, Kim J (2004) RpS3, a DNA repair endonuclease and ribosomal protein, is involved in apoptosis. FEBS Lett 560:81–85. doi:10.1016/S0014-5793(04)00074-2

    Article  PubMed  CAS  Google Scholar 

  35. Jung SO, Lee JY, Kim J (2001) Yeast ribosomal protein S3 has an endonuclease activity on AP DNA. Mol Cells 12:84–90

    PubMed  CAS  Google Scholar 

  36. Kim J, Chubatsu LS, Admon A, Stahl J, Fellous R, Linn S (1995) Implication of mammalian ribosomal protein S3 in the processing of DNA damage. J Biol Chem 270:13620–13629. doi:10.1074/jbc.270.23.13620

    Article  PubMed  CAS  Google Scholar 

  37. Kim SH, Lee JY, Kim J (2005) Characterization of a wide range base-damage-endonuclease activity of mammalian rpS3. Biochem Biophys Res Commun 328:962–967. doi:10.1016/j.bbrc.2005.01.045

    Article  PubMed  CAS  Google Scholar 

  38. Pogue-Geile K, Geiser JR, Shu M, Miller C, Wool IG, Meisler AI, Pipas JM (1991) Ribosomal protein genes are overexpressed in colorectal cancer: isolation of a cDNA clone encoding the human S3 ribosomal protein. Mol Cell Biol 11:3842–3849

    PubMed  CAS  Google Scholar 

  39. Kim SH, Kim J (2006) Reduction of invasion in human fibrosarcoma cells by ribosomal protein S3 in conjunction with Nm23-H1 and ERK. Biochim Biophys Acta - Mol Cell Res 1763:823–832. doi:10.1016/j.bbamcr.2006.03.011

    Article  CAS  Google Scholar 

  40. Genersch E, Hayess K, Neuenfeld Y, Haller H (2000) Sustained ERK phosphorylation is necessary but not sufficient for MMP-9 regulation in endothelial cells: involvement of Ras-dependent and -independent pathways. J Cell Sci 113(Pt 23):4319–4330

    PubMed  CAS  Google Scholar 

  41. Zhong J, Gencay MM, Bubendorf L, Burgess JK, Parson H, Robinson BW, Tamm M, Black JL, Roth M (2006) ERK1/2 and p38 MAP kinase control MMP-2, MT1-MMP, and TIMP action and affect cell migration: a comparison between mesothelioma and mesothelial cells. J Cell Physiol 207:540–552. doi:10.1002/jcp.20605

    Article  PubMed  CAS  Google Scholar 

  42. Kim HD, Lee JY, Kim J (2005) Erk phosphorylates threonine 42 residue of ribosomal protein S3. Biochem Biophys Res Commun 333:110–115. doi:10.1016/j.bbrc.2005.05.079

    Article  PubMed  CAS  Google Scholar 

  43. Beranova-Giorgianni S, Zhao Y, Desiderio DM, Giorgianni F (2006) Phosphoproteomic analysis of the human pituitary. Pituitary 9:109–120. doi:10.1007/s11102-006-8916-x

    Article  PubMed  CAS  Google Scholar 

  44. Kim TS, Kim HD, Kim J (2009) PKCdelta-dependent functional switch of rpS3 between translation and DNA repair. Biochim Biophys Acta - Mol Cell Res 1793:395–405. doi:10.1016/j.bbamcr.2008.10.017

    Article  CAS  Google Scholar 

  45. Crawford RM, Treharne KJ, Arnaud-Dabernat S, Daniel JY, Foretz M, Viollet B, Mehta A (2006) Understanding the molecular basis of the interaction between NDPK-A and AMPK alpha 1. Mol Cell Biol 26:5921–5931. doi:10.1128/MCB.00315-06

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported in part by Proteomics FPR05C2-390 grant, RO1-2008-000-11574, and 2006-02293 DNA repair grant.

Author information

Authors and Affiliations

  1. School of Life Sciences & Biotechnology, and BioInstitute, Korea University, Seoul, 136-713, Korea

    Hag Dong Kim, Tae-Sung Kim, Sang-Hwa Kim, Hyun-Seock Shin & Joon Kim

  2. Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan, 609-735, Korea

    BuHyun Youn

Authors
  1. Hag Dong Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. BuHyun Youn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tae-Sung Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sang-Hwa Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hyun-Seock Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Joon Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joon Kim.

Additional information

Hag Dong Kim and BuHyun Youn have contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, H.D., Youn, B., Kim, TS. et al. Regulators affecting the metastasis suppressor activity of Nm23-H1. Mol Cell Biochem 329, 167–173 (2009). https://doi.org/10.1007/s11010-009-0109-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-009-0109-2

Keywords

Search

Navigation