Skip to main content
SpringerLink
Log in

Translation Factor eIF5A, Modification with Hypusine and Role in Regulation of Gene Expression. eIF5A as a Target for Pharmacological Interventions

  • Review
  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

Translation factor eIF5A participates in protein synthesis at the stage of polypeptide chain elongation. Two eIF5A isoforms are known that are encoded by related genes whose expression varies significantly in different tissues. The eIF5A1 isoform is a constitutively and ubiquitously expressed gene, while the eIF5A2 isoform is expressed in few normal tissues and is an oncogene by a number of parameters. Unique feature of eIF5A isoforms is that they are the only two proteins that contain amino acid hypusine. Modification with hypusine is critical requirement for eIF5A activity. Another distinctive feature of eIF5A is its involvement in the translation of only a subset of the total population of cell mRNAs. The genes for which mRNAs translation requires eIF5A are the members of certain functional groups and are involved in cell proliferation, apoptosis, inflammatory processes, and regulation of transcription and RNA metabolism. The involvement of eIF5A is necessary for the translation of proteins containing oligoproline fragments and some other structures. Modification of eIF5A by hypusine is implemented by two highly specialized enzymes, deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH), which are not involved in other biochemical reactions. Intracellular activity of these enzymes is closely associated with systems of protein acetylation, polyamine metabolism and other biochemical processes. Inhibition of DHS and DOHH activity provides the possibility of pharmacological control of eIF5A activity and expression of eIF5A-dependent genes.

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

Abbreviations

DFMO:

difluoromethylornithine

DHS:

deoxyhypusine synthase

DOHH:

deoxyhypusine hydroxylase

eIF5A:

eukaryotic translation initiation factor 5A

eIF5A(Dhp):

deoxyhypusine–modified eIF5A

eIF5A(Hyp):

hypusine–modified eIF5A

eIF5A(Lys):

unmodified eIF5A

GC7:

N1–guanyl–1,7–diaminoheptane

iNOS:

inducible nitric oxide synthase

shRNA:

small hairpin RNA

References

  1. Merrick, W. C., and Anderson, W. F. (1975) Purification and characterization of homogeneous protein synthesis initiation factor M1 from rabbit reticulocytes, J. Biol. Chem., 250, 1197–1206.

    PubMed  CAS  Google Scholar 

  2. Cooper, H. L., Park, M. H., and Folk, J. E. (1982) Post–translational formation of hypusine in a single major protein occurs generally in growing cells and is associated with activation of lymphocyte growth, Cell, 29, 791–797.

    Article  PubMed  CAS  Google Scholar 

  3. Jenkins, Z. A., Haag, P. G., and Johansson, H. E. (2001) Human eIF5A2 on chromosome 3q25–q27 is a phylogenetically conserved vertebrate variant of eukaryotic translation initiation factor 5A with tissue–specific expression, Genomics, 71, 101–109.

    Article  PubMed  CAS  Google Scholar 

  4. Caraglia, M., Park, M. H., Wolff, E. C., Marra, M., and Abbruzzese, A. (2013) eIF5A isoforms and cancer: two brothers for two functions? Amino Acids, 44, 103–109.

    Article  PubMed  CAS  Google Scholar 

  5. Dever, T. E., Gutierrez, E., and Shin, B. S. (2014) The hypusine–containing translation factor eIF5A, Crit. Rev. Biochem. Mol. Biol., 49, 413–425.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Meng, Q. B., Kang, W. M., Yu, J. C., Liu, Y. Q., Ma, Z. Q., Zhou, L., Cui, Q. C., and Zhou, W. X. (2015) The hypusine–containing translation factor eIF5A, PLoS One, 10, e0119229.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Nishimura, K., Lee, S. B., Park, J. H., and Park, M. H. (2012) Essential role of eIF5A–1 and deoxyhypusine synthase in mouse embryonic development, Amino Acids, 42, 703–710.

    Article  PubMed  CAS  Google Scholar 

  8. Benne, R., Brown–Luedi, M. L., and Hershey, J. W. (1978) Purification and characterization of protein synthesis initiation factors eIF–1, eIF–4C, eIF–4D, and eIF–5 from rabbit reticulocytes, J. Biol. Chem., 253, 3070–3077.

    PubMed  CAS  Google Scholar 

  9. Rossi, D., Barbosa, N. M., Galvao, F. C., Boldrin, P. E., Hershey, J. W., Zanelli, C. F., Fraser, C. S., and Valentini, S. R. (2016) Evidence for a negative cooperativity between eIF5A and eEF2 on binding to the ribosome, PLoS One, 11, e0154205.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Dias, C. A., Gregio, A. P., Rossi, D., Galvao, F. C., Watanabe, T. F., Park, M. H., Valentini, S. R., and Zanelli, C. F. (2012) eIF5A interacts functionally with eEF2, Amino Acids, 42, 697–702.

    Article  PubMed  CAS  Google Scholar 

  11. Schmidt, C., Becker, T., Heuer, A., Braunger, K., Shanmuganathan, V., Pech, M., Berninghausen, O., Wilson, D. N., and Beckmann, R. (2016) Structure of the hypusinylated eukaryotic translation factor eIF–5A bound to the ribosome, Nucleic Acids Res., 44, 1944–1951.

    Article  PubMed  Google Scholar 

  12. Schuller, A. P., Wu, C. C., Dever, T. E., Buskirk, A. R., and Green, R. (2017) eIF5A functions globally in translation elongation and termination, Mol. Cell, 66, 194–205.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Pelechano, V., and Alepuz, P. (2017) eIF5A facilitates translation termination globally and promotes the elongation of many non–polyproline–specific tripeptide sequences, Nucleic Acids Res., 45, 7326–7338.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Rossi, D., Galvao, F. C., Bellato, H. M., Boldrin, P. E., Andrews, B. J., Valentini, S. R., and Zanelli, C. F. (2014) eIF5A has a function in the cotranslational translocation of proteins into the ER, Amino Acids, 46, 645–653.

    Article  PubMed  CAS  Google Scholar 

  15. Hauber, J. (2010) Revisiting an old acquaintance: role for eIF5A in diabetes, J. Clin. Invest., 120, 1806–1808.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Nishiki, Y., Adewola, A., Hatanaka, M., Templin, A. T., Maier, B., and Mirmira, R. G. (2013) Translational control of inducible nitric oxide synthase by p38 MAPK in islet β–cells, Mol. Endocrinol., 27, 336–349.

    Article  PubMed  CAS  Google Scholar 

  17. Mandal, A., Mandal, S., and Park, M. H. (2016) Global quantitative proteomics reveal up–regulation of endoplasmic reticulum stress response proteins upon depletion of eIF5A in HeLa cells, Sci. Rep., 6, 25795.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Gutierrez, E., Shin, B. S., Woolstenhulme, C. J., Kim, J. R., Saini, P., Buskirk, A. R., and Dever, T. E. (2013) eIF5A promotes translation of polyproline motifs, Mol. Cell, 51, 35–45.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Wohlgemuth, I., Brenner, S., Beringer, M., and Rodnina, M. V. (2008) Modulation of the rate of peptidyl transfer on the ribosome by the nature of substrates, J. Biol. Chem., 283, 32229–32235.

    Article  PubMed  CAS  Google Scholar 

  20. Pavlov, M. Y., Watts, R. E., Tan, Z., Cornish, V. W., Ehrenberg, M., and Forster, A. C. (2009) Slow peptide bond formation by proline and other N–alkylamino acids in translation, Proc. Natl. Acad. Sci. USA, 106, 50–54.

    Article  PubMed  Google Scholar 

  21. Henderson, A., and Hershey, J. W. (2011) Eukaryotic translation initiation factor (eIF) 5A stimulates protein synthesis in Saccharomyces cerevisiae, Proc. Natl. Acad. Sci. USA, 108, 6415–6419.

    Article  PubMed  Google Scholar 

  22. Zarrinpar, A., Bhattacharyya, R. P., and Lim, W. A. (2003) The structure and function of proline recognition domains, Sci. STKE, 2003, RE8.

    Google Scholar 

  23. Mandal, A., Mandal, S., and Park, M. H. (2014) Genome–wide analyses and functional classification of proline repeat–rich proteins: potential role of eIF5A in eukaryotic evolution, PLoS One, 9, e111800.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Kaiser, A. (2012) Translational control of eIF5A in various diseases, Amino Acids, 42, 679–684.

    Article  PubMed  CAS  Google Scholar 

  25. Mathews, M. B., and Hershey, J. W. (2015) The translation factor eIF5A and human cancer, Biochim. Biophys. Acta, 1849, 836–844.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Fujimura, K., Choi, S., Wyse, M., Strnadel, J., Wright, T., and Klemke, R. (2015) Eukaryotic translation initiation factor 5A (EIF5A) regulates pancreatic cancer metastasis by modulating RhoA and Rho–associated kinase (ROCK) protein expression levels, J. Biol. Chem., 290, 29907–29919.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Memin, E., Hoque, M., Jain, M. R., Heller, D. S., Li, H., Cracchiolo, B., Hanauske–Abel, H. M., Pe’ery, T., and Mathews, M. B. (2014) Blocking eIF5A modification in cervical cancer cells alters the expression of cancer–related genes and suppresses cell proliferation, Cancer Res., 74, 552–562.

    Article  PubMed  CAS  Google Scholar 

  28. Park, M. H., Cooper, H. L., and Folk, J. E. (1981) Identification of hypusine, an unusual amino acid, in a protein from human lymphocytes and of spermidine as its biosynthetic precursor, Proc. Natl. Acad. Sci. USA, 78, 2869–2873.

    Article  PubMed  CAS  Google Scholar 

  29. Shiba, T., Mizote, H., Kaneko, T., Nakajima, T., and Kakimoto, Y. (1971) Hypusine, a new amino acid occurring in bovine brain. Isolation and structural determination, Biochim. Biophys. Acta, 244, 523–531.

    Article  PubMed  CAS  Google Scholar 

  30. Tersey, S. A., Colvin, S. C., Maier, B., and Mirmira, R. G. (2014) Protective effects of polyamine depletion in mouse models of type 1 diabetes: implications for therapy, Amino Acids, 46, 633–642.

    Article  PubMed  CAS  Google Scholar 

  31. Abbruzzese, A., Park, M. H., and Folk, J. E. (1986) Deoxyhypusine hydroxylase from rat testis. Partial purification and characterization, J. Biol. Chem., 261, 3085–3089.

    PubMed  CAS  Google Scholar 

  32. Han, Z., Sakai, N., Bottger, L. H., Klinke, S., Hauber, J., Trautwein, A. X., and Hilgenfeld, R. (2015) Crystal structure of the peroxo–diiron(III) intermediate of deoxyhypusine hydroxylase, an oxygenase involved in hypusination, Structure, 23, 882–892.

    Article  PubMed  CAS  Google Scholar 

  33. Frey, A. G., Nandal, A., Park, J. H., Smith, P. M., Yabe, T., Ryu, M. S., Ghosh, M. C., Lee, J., Rouault, T. A., Park, M. H., and Philpott, C. C. (2014) Iron chaperones PCBP1 and PCBP2 mediate the metallation of the dinuclear iron enzyme deoxyhypusine hydroxylase, Proc. Natl. Acad. Sci. USA, 111, 8031–8036.

    Article  PubMed  CAS  Google Scholar 

  34. Park, M. H., Mandal, A., Mandal, S., and Wolff, E. C. (2017) A new non–radioactive deoxyhypusine synthase assay adaptable to high throughput screening, Amino Acids, 49, 1793–1804.

    Article  PubMed  CAS  Google Scholar 

  35. Ishfaq, M., Maeta, K., Maeda, S., Natsume, T., Ito, A., and Yoshida, M. (2012) Acetylation regulates subcellular localization of eukaryotic translation initiation factor 5A (eIF5A), FEBS Lett., 586, 3236–3241.

    Article  PubMed  CAS  Google Scholar 

  36. Maier, B., Ogihara, T., Trace, A. P., Tersey, S. A., Robbins, R. D., Chakrabarti, S. K., Nunemaker, C. S., Stull, N. D., Taylor, C. A., Thompson, J. E., Dondero, R. S., Lewis, E. C., Dinarello, C. A., Nadler, J. L., and Mirmira, R. G. (2010) The unique hypusine modification of eIF5A promotes islet beta cell inflammation and dysfunction in mice, J. Clin. Invest., 120, 2156–2170.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Park, J. H., Wolff, E. C., Folk, J. E., and Park, M. H. (2003) Reversal of the deoxyhypusine synthesis reaction. Generation of spermidine or homospermidine from deoxyhypusine by deoxyhypusine synthase, J. Biol. Chem., 278, 32683–32691.

    Article  PubMed  CAS  Google Scholar 

  38. Sievert, H., Pallmann, N., Miller, K. K., Hermans–Borgmeyer, I., Venz, S., Sendoel, A., Preukschas, M., Schweizer, M., Boettcher, S., Janiesch, P. C., Streichert, T., Walther, R., Hengartner, M. O., Manz, M. G., Brummendorf, T. H., Bokemeyer, C., Braig, M., Hauber, J., Duncan, K. E., and Balabanov, S. (2014) A novel mouse model for inhibition of DOHH–mediated hypusine modification reveals a crucial function in embryonic development, proliferation and oncogenic transformation, Dis. Model. Mech., 7, 963–976.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Li, C. H., Ohn, T., Ivanov, P., Tisdale, S., and Anderson, P. (2010) eIF5A promotes translation elongation, polysome disassembly and stress granule assembly, PLoS One, 5, e9942.

    Google Scholar 

  40. Lee, W. B., Kang, J. S., Choi, W. Y., Zhang, Q., Kim, C. H., Choi, U. Y., Kim–Ha, J., and Kim, Y. J. (2016) Mincle–mediated translational regulation is required for strong nitric oxide production and inflammation resolution, Nat. Commun., 7, 11322.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Lewandowska–Gnatowska, E., Szymona, L., Lebska, M., Szczegielniak, J., and Muszynska, G. (2011) Phosphorylation of maize eukaryotic translation initiation factor on Ser2 by catalytic subunit CK2, Mol. Cell. Biochem., 356, 241–244.

    Article  PubMed  CAS  Google Scholar 

  42. Beninati, S., Gentile, V., Caraglia, M., Lentini, A., Tagliaferri, P., and Abbruzzese, A. (1998) Tissue transglutaminase expression affects hypusine metabolism in BALB/c 3T3 cells, FEBS Lett., 437, 34–38.

    Article  PubMed  CAS  Google Scholar 

  43. Ishfaq, M., Maeta, K., Maeda, S., Natsume, T., Ito, A., and Yoshida, M. (2012) The role of acetylation in the sub–cellular localization of an oncogenic isoform of translation factor eIF5A, Biosci. Biotechnol. Biochem., 76, 2165–2167.

    Article  PubMed  CAS  Google Scholar 

  44. Shah, A. A., Ito, A., Nakata, A., and Yoshida, M. (2016) Identification of a selective SIRT2 inhibitor and its anti–breast cancer activity, Biol. Pharm. Bull., 39, 1739–1742.

    Article  PubMed  CAS  Google Scholar 

  45. Pallmann, N., Braig, M., Sievert, H., Preukschas, M., Hermans–Borgmeyer, I., Schweizer, M., Nagel, C. H., Neumann, M., Wild, P., Haralambieva, E., Hagel, C., Bokemeyer, C., Hauber, J., and Balabanov, S. (2015) Biological relevance and therapeutic potential of the hypusine modification system, J. Biol. Chem., 290, 18343–18360.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Tariq, M., Ito, A., Ishfaq, M., Bradshaw, E., and Yoshida, M. (2016) Eukaryotic translation initiation factor 5A (eIF5A) is essential for HIF–1α activation in hypoxia, Biochem. Biophys. Res. Commun., 470, 417–424.

    Article  PubMed  CAS  Google Scholar 

  47. Sun, Z., Cheng, Z., Taylor, C. A., McConkey, B. J., and Thompson, J. E. (2010) Apoptosis induction by eIF5A1 involves activation of the intrinsic mitochondrial pathway, J. Cell. Physiol., 223, 798–809.

    PubMed  CAS  Google Scholar 

  48. Clement, P. M., Johansson, H. E., Wolff, E. C., and Park, M. H. (2006) Differential expression of eIF5A–1 and eIF5A–2 in human cancer cells, FEBS J., 273, 1102–1114.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Park, J. H., Johansson, H. E., Aoki, H., Huang, B. X., Kim, H. Y., Ganoza, M. C., and Park, M. H. (2012) Post–translational modification by β–lysylation is required for activity of Escherichia coli elongation factor P (EF–P), J. Biol. Chem., 287, 2579–2590.

    Article  PubMed  CAS  Google Scholar 

  50. Doerfel, L. K., Wohlgemuth, I., Kothe, C., Peske, F., Urlaub, H., and Rodnina, M. V. (2013) EF–P is essential for rapid synthesis of proteins containing consecutive proline residues, Science, 339, 85–88.

    Article  PubMed  CAS  Google Scholar 

  51. Greganova, E., Altmann, M., and Butikofer, P. (2011) Unique modifications of translation elongation factors, FEBS J., 278, 2613–2624.

    Article  PubMed  CAS  Google Scholar 

  52. Hershey, J. W. (1994) Expression of initiation factor genes in mammalian cells, Biochimie, 76, 847–852.

    Article  PubMed  CAS  Google Scholar 

  53. Kulak, N. A., Pichler, G., Paron, I., Nagaraj, N., and Mann, M. (2014) Minimal, encapsulated proteomic–sample processing applied to copy–number estimation in eukaryotic cells, Nat. Methods, 11, 319–324.

    Article  PubMed  CAS  Google Scholar 

  54. Nakanishi, S., and Cleveland, J. L. (2016) Targeting the polyamine–hypusine circuit for the prevention and treatment of cancer, Amino Acids, 48, 2353–2362.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Hoque, M., Hanauske–Abel, H. M., Palumbo, P., Saxena, D., D’Alliessi Gandolfi, D., Park, M. H., Pe’ery, T., and Mathews, M. B. (2009) Inhibition of HIV–1 gene expression by Ciclopirox and Deferiprone, drugs that prevent hypusination of eukaryotic initiation factor 5A, Retrovirology, 6, 90.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Templin, A. T., Maier, B., Nishiki, Y., Tersey, S. A., and Mirmira, R. G. (2011) Deoxyhypusine synthase haploin–sufficiency attenuates acute cytokine signaling, Cell Cycle, 10, 1043–1049.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Nguyen, S., Leija, C., Kinch, L., Regmi, S., Li, Q., Grishin, N. V., and Phillips, M. A. (2015) Deoxyhypusine modification of eukaryotic translation initiation factor 5A (eIF5A) is essential for Trypanosoma brucei growth and for expression of polyprolyl–containing proteins, J. Biol. Chem., 290, 19987–19998.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Clement, P. M., Hanauske–Abel, H. M., Wolff, E. C., Kleinman, H. K., and Park, M. H. (2002) The antifungal drug ciclopirox inhibits deoxyhypusine and proline hydroxylation, endothelial cell growth and angiogenesis in vitro, Int. J. Cancer, 100, 491–498.

    Article  PubMed  CAS  Google Scholar 

  59. Hyvonen, M. T., Khomutov, M., Petit, M., Weisell, J., Kochetkov, S. N., Alhonen, L., Vepsalainen, J., Khomutov, A. R., and Keinanen, T. A. (2015) Enantiomers of 3–methylspermidine selectively modulate deoxyhypusine synthesis and reveal important determinants for spermidine transport, ACS Chem. Biol., 10, 1417–1424.

    Article  PubMed  CAS  Google Scholar 

  60. Jakus, J., Wolff, E. C., Park, M. H., and Folk, J. E. (1993) Features of the spermidine–binding site of deoxyhypusine synthase as derived from inhibition studies. Effective inhibition by bis– and mono–guanylated diamines and polyamines, J. Biol. Chem., 268, 13151–13159.

    PubMed  CAS  Google Scholar 

  61. Bianchi, M., Ulrich, P., Bloom, O., Meistrell, M., Zimmerman, G. A., Schmidtmayerova, H., Bukrinsky, M., Donnelley, T., Bucala, R., and Sherry, B. (1995) An inhibitor of macrophage arginine transport and nitric oxide production (CNI–1493) prevents acute inflammation and endotoxin lethality, Mol. Med., 1, 254–266.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Kawada, M., Masuda, T., Ishizuka, M., and Takeuchi, T. (2002) 15–Deoxyspergualin inhibits Akt kinase activation and phosphatidylcholine synthesis, J. Biol. Chem., 277, 27765–27771.

    Article  PubMed  CAS  Google Scholar 

  63. Shen, T., and Huang, S. (2016) Repositioning the old fungicide ciclopirox for new medical uses, Curr. Pharm. Des., 22, 4443–4450.

    Article  PubMed  CAS  Google Scholar 

  64. Robbins, R. D., Tersey, S. A., Ogihara, T., Gupta, D., Farb, T. B., Ficorilli, J., Bokvist, K., Maier, B., and Mirmira, R. G. (2010) Inhibition of deoxyhypusine synthase enhances islet β cell function and survival in the setting of endoplasmic reticulum stress and type 2 diabetes, J. Biol. Chem., 285, 39943–39952.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Gosslau, A., Jao, D. L., Butler, R., Liu, A. Y., and Chen, K. Y. (2009) Thermal killing of human colon cancer cells is associated with the loss of eukaryotic initiation factor 5A, J. Cell. Physiol., 219, 485–493.

    Article  PubMed  CAS  Google Scholar 

  66. Ziegler, P., Chahoud, T., Wilhelm, T., Pallman, N., Braig, M., Wiehle, V., Ziegler, S., Schroder, M., Meier, C., Kolodzik, A., Rarey, M., Panse, J., Hauber, J., Balabanov, S., and Brummendorf, T. H. (2012) Evaluation of deoxyhypusine synthase inhibitors targeting BCR–ABL positive leukemias, Invest. New Drugs, 30, 2274–2283.

    Article  PubMed  CAS  Google Scholar 

  67. Mokhtari, D., Al–Amin, A., Turpaev, K., Li, T., Idevall–Hagren, O., Li, J., Wuttke, A., Fred, R. G., Ravassard, P., Scharfmann, R., Tengholm, A., and Welsh, N. (2013) Imatinib mesilate–induced phosphatidylinositol–3–kinase signaling and improved survival in insulin–producing cells: role of Src homology 2–containing inositol 5′–phosphatase interaction with c–Abl, Diabetologia, 56, 1327–1338.

    Article  PubMed  CAS  Google Scholar 

  68. Muramatsu, T., Kozaki, K. I., Imoto, S., Yamaguchi, R., Tsuda, H., Kawano, T., Fujiwara, N., Morishita, M., Miyano, S., and Inazawa, J. (2016) The hypusine cascade promotes cancer progression and metastasis through the regulation of RhoA in squamous cell carcinoma, Oncogene, 35, 5304–5316.

    Article  PubMed  CAS  Google Scholar 

  69. Colvin, S. C., Maier, B., Morris, D. L., Tersey, S. A., and Mirmira, R. G. (2013) Deoxyhypusine synthase promotes differentiation and proliferation of T helper type 1 (Th1) cells in autoimmune diabetes, J. Biol. Chem., 288, 36226–36235.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. De Almeida, O. P., Toledo, T. R., Rossi, D., de Barros Rossetto, D., Watanabe, T. F., Galvao, F. C., Medeiros, A. I., Zanelli, C. F., and Valentini, S. R. (2014) Hypusine modification of the ribosome–binding protein eIF5A, a target for new anti–inflammatory drugs: understanding the action of the inhibitor GC7 on a murine macrophage cell line, Curr. Pharm. Des., 20, 284–292.

    Article  PubMed  CAS  Google Scholar 

  71. Bandino, A., Geerts, D., Koster, J., and Bachmann, A. S. (2014) Deoxyhypusine synthase (DHPS) inhibitor GC7 induces p21/Rb–mediated inhibition of tumor cell growth and DHPS expression correlates with poor prognosis in neuroblastoma patients, Cell. Oncol. (Dordrecht), 37, 387–398.

    Article  CAS  Google Scholar 

  72. Xue, F., Liu, Y., Chu, H., Wen, Y., Yan, L., Tang, Q., Xiao, E., Zhang, D., and Zhang, H. (2016) eIF5A2 is an alternative pathway for cell proliferation in cetuximab–treated epithelial hepatocellular carcinoma, Am. J. Transl. Res., 8, 4670–4681.

    PubMed  PubMed Central  CAS  Google Scholar 

  73. Caraglia, M., Marra, M., Giuberti, G., D’Alessandro, A. M., Baldi, A., Tassone, P., Venuta, S., Tagliaferri, P., and Abbruzzese, A. (2003) The eukaryotic initiation factor 5A is involved in the regulation of proliferation and apoptosis induced by interferon–alpha and EGF in human cancer cells, J. Biochem., 133, 757–765.

    Article  PubMed  CAS  Google Scholar 

  74. Fang, L., Gao, L., Xie, L., and Xiao, G. (2018) GC7 enhances cisplatin sensitivity via STAT3 signaling pathway inhibition and eIF5A2 inactivation in mesenchymal phenotype oral cancer cells, Oncol. Rep., 39, 1283–1291.

    PubMed  Google Scholar 

  75. Schultz, C. R., Geerts, D., Mooney, M., El–Khawaja, R., Koster, J., and Bachmann, A. S. (2018) Synergistic drug combination GC7/DFMO suppresses hypusine/spermi–dine–dependent eIF5A activation and induces apoptotic cell death in neuroblastoma, Biochem. J., 475, 531–545.

    Article  PubMed  CAS  Google Scholar 

  76. Cao, T. T., Lin, S. H., Fu, L., Tang, Z., Che, C. M., Zhang, L. Y., Ming, X. Y., Liu, T. F., Tang, X. M., Tan, B. B., Xiang, D., Li, F., Chan, O. Y., Xie, D., Cai, Z., and Guan, X. Y. (2017) Eukaryotic translation initiation factor 5A2 promotes metabolic reprogramming in hepatocellular carcinoma cells, Carcinogenesis, 38, 94–104.

    Article  PubMed  CAS  Google Scholar 

  77. Khosravi, S., Martinka, M., Zhou, Y., and Ong, C. J. (2016) Prognostic significance of the expression of nuclear eukaryotic translation initiation factor 5A2 in human melanoma, Oncol. Lett., 12, 3089–3100.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, 119991, Moscow, Russia

    K. T. Turpaev

Authors
  1. K. T. Turpaev
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K. T. Turpaev.

Additional information

Original Russian Text © K. T. Turpaev, 2018, published in Biokhimiya, 2018, Vol. 83, No. 8, pp. 1099–1110.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Turpaev, K.T. Translation Factor eIF5A, Modification with Hypusine and Role in Regulation of Gene Expression. eIF5A as a Target for Pharmacological Interventions. Biochemistry Moscow 83, 863–873 (2018). https://doi.org/10.1134/S0006297918080011

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297918080011

Keywords

Search

Navigation