Translational Initiation of Ornithine Decarboxylase mRNA

  • Lo Persson
  • Koichi Takao
Part of the Endocrine Updates book series (ENDO, volume 16)


The polyamines (putrescine, spermidine and spermine) are a group of small intracellular aliphatic amines essential for a variety of growth-related processes in the cell. The importance of the polyamines in cell function is reflected in a strict regulatory control of their intracellular levels. High polyamine concentration can be toxic to the cell, whereas low concentrations may negatively affect anabolic events such as the synthesis of DNA, RNA and protein, eventually giving rise to cell growth arrest. Ornithine decarboxylase (ODC) catalyzes the first and what is often considered as the rate-limiting step in the biosynthesis of the polyamines. The enzyme is highly regulated at a multitude of levels, including the translational level. Some of the mechanisms involved in the regulation of ODC are unique and resembling those found in the control of various protooncogenes. Due to the extremely fast turnover of ODC (half-life of minutes to an hour), the cellular level of ODC protein and thus the enzyme activity is rapidly altered when the synthesis and/or degradation of the enzyme is changed.


Ornithine Decarboxylase Hypotonic Shock Ribosomal Frameshifting Strong Secondary Structure Ornithine Decarboxylase Antizyme 
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  1. 1.
    Heby O., Persson L. 1990 Molecular genetics of polyamine synthesis in eukaryotic cells. Trends Biochem Sci 15: 153–8PubMedCrossRefGoogle Scholar
  2. 2.
    Law G.L., Li R.S., Morris D.R. 1995 “Transcriptional control of the ODC gene.” In Polyamines: regulation and molecular interaction, R. A. Casero Jr, ed. Austin: R.G. Landes Company, 5–26Google Scholar
  3. 3.
    Persson L., Svensson F., Lövkvist Wallström E. 1996 “Regulation of polyamine metabolism.” In Polyamines in cancer: basic mechanisms and clinical approaches, K. Nishioka, ed. Austin: R.G. Landes Company, 19–43Google Scholar
  4. 4.
    Hayashi S., Murakami Y., Matsufuji S. 19960rnithine decarboxylase antizyme: A novel type of regulatory protein. Trends Biochem Sci 21: 27–30Google Scholar
  5. 5.
    Poulin R., Pegg A.E. 1990 Regulation of ornithine decarboxylase expression by anisosmotic shock in difluoromethylornithine-resistant L1210 cells. J Biol Chem 265: 4025–32PubMedGoogle Scholar
  6. 6.
    Lundgren D.W. 1992 Effect of hypotonic stress on ornithine decarboxylase mRNA expression in cultured cells. J Biol Chem 267: 6841–7PubMedGoogle Scholar
  7. 7.
    Lövkvist-Wallström E., Stjernborg-Ulvsbäck L., Scheffler I.E., Persson L. 1995 Regulation of mammalian ornithine decarboxylase–Studies on the induction of the enzyme by hypotonic stress. Eur J Biochem 231: 40–4PubMedCrossRefGoogle Scholar
  8. 8.
    McCann P.P., Pegg A.E. 1992 Ornithine decarboxylase as an enzyme target for therapy. Pharmacol Ther 54: 195–215PubMedCrossRefGoogle Scholar
  9. 9.
    Barrett S.V., Barrett M.P. 2000 Anti-sleeping sickness drugs and cancer chemotherapy. Parasitol Today 16: 7–9PubMedCrossRefGoogle Scholar
  10. 10.
    Kozak M. 1987 An analysis of 5’-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res 15: 8125–48PubMedCrossRefGoogle Scholar
  11. 11.
    Brabant M., McConlogue L., van Daalen Wetters T., Coffino P. 1988 Mouse ornithine decarboxylase gene: cloning, structure, and expression. Proc Natl Acad Sci USA 85: 2200–4PubMedCrossRefGoogle Scholar
  12. 12.
    Grens A., Scheffler I.E. 1990 The 5’- and 3’-untranslated regions of ornithine decarboxylase mRNA affect the translational efficiency. J Biol Chem 265: 11810–6PubMedGoogle Scholar
  13. 13.
    Manzella J.M., Blackshear P.J. 1990 Regulation of rat ornithine decarboxylase mRNA translation by its 5’-untranslated region. J Biol Chem 265: 11817–22PubMedGoogle Scholar
  14. 14.
    Lorenzini E.C., Scheffler I.E. 1997 Co-operation of the 5’ and 3’ untranslated regions of ornithine decarboxylase mRNA and inhibitory role of its 3’ untranslated region in regulating the translational efficiency of hybrid RNA species via cellular factor(s). Biochem J 326: 361–7PubMedGoogle Scholar
  15. 15.
    Manzella J.M., Blackshear P.J. 1992 Specific protein binding to a conserved region of the ornithine decarboxylase mRNA 5’-untranslated region. J Biol Chem 267: 7077–82PubMedGoogle Scholar
  16. 16.
    Holm I., Persson L., Stjemborg L., Thorsson L., Heby 0. 1989 Feedback control of ornithine decarboxylase expression by polyamines. Analysis of ornithine decarboxylase mRNA distribution in polysome profiles and of translation of this mRNA in vitro. Biochem J 258: 343–50Google Scholar
  17. 17.
    van Daalen Wetters T., Macrae M., Brabant M., Siffler A., Coffin P. 1989 Polyamine-mediated regulation of mouse ornithine decarboxylase is post-translational. Mol Cell Biol 9: 5484–90Google Scholar
  18. 18.
    Kahana C., Nathans D. 1985 Nucleotide sequence of murine ornithine decarboxylase mRNA. Proc Natl Acad Sci USA 82: 1673–7PubMedCrossRefGoogle Scholar
  19. 19.
    Pain V.M. 1996 Initiation of protein synthesis in eukaryotic cells. Eur J Biochem 236: 747–71PubMedCrossRefGoogle Scholar
  20. 20.
    Kozak M. 1999 Initiation of translation in prokaryotes and eukaryotes. Gene 234: 187–208PubMedCrossRefGoogle Scholar
  21. 21.
    Kozak M. 1989 Circumstances and mechanisms of inhibition of translation by secondary structure in eucaryotic mRNAs. Mol Cell Biol 9: 5134–42PubMedGoogle Scholar
  22. 22.
    McKendrick L., Pain V.M., Morley S.J. 1999 Translation initiation factor 4E. Int J Biochem Cell Biol 31: 31–5PubMedCrossRefGoogle Scholar
  23. 23.
    Koromilas A.E., Lazaris-Karatzas A., Sonenberg N. 1992 mRNAs containing extensive secondary structure in their 5’ non-coding region translate efficiently in cells overexpressing initiation factor eIF-4E. EMBO J 11: 4153–8Google Scholar
  24. 24.
    Polunovsky V.A., Rosenwald I.B., Tan A.T., White J., Chiang L., Sonenberg N., Bitterman P.B. 1996 Translational control of programmed cell death: eukaryotic translation initiation factor 4E blocks apoptosis in growth-factor-restricted fibroblasts with physiologically expressed or deregulated Myc. Mol Cell Biol 16: 6573–81PubMedGoogle Scholar
  25. 25.
    Raught B., Gingras A.C. 1999 eIF4E activity is regulated at multiple levels. Int J Biochem Cell Biol 31: 43–57Google Scholar
  26. 26.
    Lazaris-Karatzas A., Montine K.S., Sonenberg N. 1990 Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA 5’ cap. Nature 345: 544–7PubMedCrossRefGoogle Scholar
  27. 27.
    Zimmer S.G., DeBenedetti A., Graff J.R. 2000 Translational control of malignancy: the mRNA cap-binding protein, eIF-4E, as a central regulator of tumor formation, growth, invasion and metastasis. Anticancer Res 20: 1343–51PubMedGoogle Scholar
  28. 28.
    Auvinén M., Paasinen A., Andersson L.C., HSltta E. 1992 Ornithine decarboxylase activity is critical for cell transformation. Nature 360: 355–8PubMedCrossRefGoogle Scholar
  29. 29.
    Rousseau D., Kaspar R., Rosenwald I., Gehrke L., Sonenberg N. 1996 Translation initiation of ornithine decarboxylase and nucleocytoplasmic transport of cyclin DI mRNA are increased in cells overexpressing eukaryotic initiation factor 4E. Proc Natl Acad Sci U S A 93: 1065–70PubMedCrossRefGoogle Scholar
  30. 30.
    Shantz L.M., Hu R.H., Pegg A.E. 1996 Regulation of ornithine decarboxylase in a transformed cell line that overexpresses translation initiation factor eIF-4E. Cancer Res 56: 3265–9PubMedGoogle Scholar
  31. 31.
    Graff J.R., De Benedetti A., Olson J.W., Tamez P., Casero R.A., Jr., Zimmer S.G. 1997 Translation of ODC mRNA and polyamine transport are suppressed in ras-transformed CREF cells by depleting translation initiation factor 4E. Biochem Biophys Res Commun 240: 15–20PubMedCrossRefGoogle Scholar
  32. 32.
    Shantz L.M., Pegg A.E. 1994 Overproduction of ornithine decarboxylase caused by relief of translational repression is associated with neoplastic transformation. Cancer Res 54: 2313–6PubMedGoogle Scholar
  33. 33.
    Shantz L.M., Coleman C.S., Pegg A.E. 1996 Expression of an ornithine decarboxylase dominant-negative mutant reverses eukaryotic initiation factor 4E-induced cell transformation. Cancer Res 56: 5136–40PubMedGoogle Scholar
  34. 34.
    Martinez-Salas E. 1999 Internal ribosome entry site biology and its use in expression vectors. Curr Opin Biotechnol 10: 458–64PubMedCrossRefGoogle Scholar
  35. 35.
    Sachs A.B. 2000 Cell cycle-dependent translation initiation: IRES elements prevail. Cell 101: 243–5PubMedCrossRefGoogle Scholar
  36. 36.
    Pelletier J., Sonenberg N. 1988 Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA. Nature 334: 320–5PubMedCrossRefGoogle Scholar
  37. 37.
    Sonenberg N. 1990 Measures and countermeasures in the modulation of initiation factor activities by viruses. New Biol 2: 402–9PubMedGoogle Scholar
  38. 38.
    van der Velden A.W., Thomas A.A. 1999 The role of the 5’ untranslated region of an mRNA in translation regulation during development. Int J Biochem Cell Biol 31: 87–106PubMedCrossRefGoogle Scholar
  39. 39.
    Pyronnet S., Pradayrol L., Sonenberg N. 2000 A cell cycle-dependent internal ribosome entry site. Mol Cell 5: 607–16PubMedCrossRefGoogle Scholar
  40. 40.
    Fredlund J.O., Johansson M.C., Dahlberg E., Oredsson S.M. 1995 Ornithine decarboxylase and S-adenosylmethionine decarboxylase expression during the cell cycle of Chinese hamster ovary cells. Exp Cell Res 216: 86–92PubMedCrossRefGoogle Scholar
  41. 41.
    Heby O., Gray J.W., Lindl P.A., Marton L.J., Wilson C.B. 1976 Changes in L-ornithine decarboxylase activity during the cell cycle. Biochem Biophys Res Commun 71: 99–105PubMedCrossRefGoogle Scholar
  42. 42.
    Fredlund J.O., Oredsson S.M. 1996 Impairment of DNA replication within one cell cycle after seeding of cells in the presence of a polyamine-biosynthesis inhibitor. Eur J Biochem 237: 539–44PubMedCrossRefGoogle Scholar
  43. 43.
    Fredlund J.O., Oredsson S.M. 1997 Ordered cell cycle phase perturbations in Chinese hamster ovary cells treated with an S-adenosylmethionine decarboxylase inhibitor. Eur J Biochem 249: 232–8PubMedCrossRefGoogle Scholar
  44. 44.
    Lövkvist Wallström E., Persson L. 1999 No role of the 5’ untranslated region of ornithine decarboxylase mRNA in the feedback control of the enzyme. Mol Cell Biochem 197: 71–8CrossRefGoogle Scholar
  45. 45.
    Hayashi S., Murakami Y. 1995 Rapid and regulated degradation of ornithine decarboxylase. Biochem J 306: 1–10PubMedGoogle Scholar
  46. 46.
    Murakami Y., Matsufuji S., Kameji T., Hayashi S., Igarashi K., Tamura T., Tanaka K., Ichihara A. 1992 Omithine decarboxylase is degraded by the 26S proteasome without ubiquitination. Nature 360: 597–9PubMedCrossRefGoogle Scholar
  47. 47.
    Miyazaki Y., Matsufuji S., Hayashi S. 1992 Cloning and characterization of a rat gene encoding ornithine decarboxylase antizyme. Gene 113: 191–7PubMedCrossRefGoogle Scholar
  48. 48.
    Rom E., Kahana C. 1994 Polyamines regulate the expression of omithine decarboxylase antizyme in vitro by inducing ribosomal frame-shifting. Proc Natl Acad Sci USA 91: 3959–63PubMedCrossRefGoogle Scholar
  49. 49.
    Matsufuji S., Matsufuji T., Miyazaki Y., Murakami Y., Atkins J.F., Gesteland R.F., Hayashi S. 1995 Autoregulatory frameshifting in decoding mammalian ornithine decarboxylase antizyme. Cell 80: 51–60PubMedCrossRefGoogle Scholar
  50. 50.
    Black B.L., Lu J., Olson E.N. 1997 The MEF2A 3’ untranslated region functions as a cis-acting translational repressor. Mol Cell Biol 17: 2756–63PubMedGoogle Scholar
  51. 51.
    Piecyk M., Wax S., Beck A.R., Kedersha N., Gupta M., Maritim B., Chen S., Gueydan C., Kruys V., Streuli M., Anderson P. 2000 TIA-1 is a translational silencer that selectively regulates the expression of TNF-alpha. EMBO J 19: 4154–63PubMedCrossRefGoogle Scholar
  52. 52.
    Mbella E.G., Bertrand S., Huez G., Octave J.N. 2000 A GG nucleotide sequence of the 3’ untranslated region of amyloid precursor protein mRNA plays a key role in the regulation of translation and the binding of proteins. Mol Cell Biol 20: 4572–9PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Lo Persson
    • 1
  • Koichi Takao
    • 2
  1. 1.University of LundLundSweden
  2. 2.Josai UniversitySaitamaJapan

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