Phosphorylation by Casein Kinase-2 and Reversible Alteration of Thiol Groups: Mechanisms of Control of Ornithine Decarboxylase?

  • Flavio Flamigni
  • Flavio Meggio
  • Sandra Marmiroli
  • Carlo Guarnieri
  • Lorenzo A. Pinna
  • Claudio M. Caldarera
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 250)


The regulation of ornithine decarboxylase (ODC) in mammalian cells appears to be complex and not completely clarified.1, 2 This enzyme is characterized by a very short half-life, but the mechanism of ODC degradation is as yet unknown3. Because of the rapid turnover, changes in the rate of synthesis are promptly expressed as fluctuations of ODC activity1, 4. However, a post-translational control of ODC has been proposed by several Authors1, and include interaction with a specific inhibitor, antizyme5, and interconversion between distinct charged species6. These mechanisms could account for the occurence of inactive ODC forms or play a function in the process of ODC decay, although their precise role remains to be defined. The present paper focuses on two additional covalent modifications of ODC molecule, which could cooperate at the control of ODC activity and decay: the reversible oxidation of sulphydrylic groups and the phosphorylation by a particular class of protein kinases, called casein kinase-2 (CK-2).


Casein Kinase Ornithine Decarboxylase Azelaic Acid Ornithine Decarboxylase Activity Thiol Redox Status 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    C.W. Tabor and H. Tabor, Polyamines, Ann. Rev. Biochem. 53: 749 (1984).PubMedCrossRefGoogle Scholar
  2. 2.
    A.E. Pegg, Recent advances in the biochemistry of polyamines in eukaryotes, Biochem. J. 234: 249 (1986).PubMedGoogle Scholar
  3. 3.
    J.R. Glass and E.W. Gerner, Spermidine mediates degradation of ornithine decarboxylase by a non-lysosomal, ubiquitinindependent mechanism, J.Cell.Physiol. 130: 133 (1987).PubMedCrossRefGoogle Scholar
  4. 4.
    D.H. Russell, Ornithine decarboxylase, a key regulatory enzyme in normal and neoplastic growth, Drug Metab.Rev 16: 1 (1985).PubMedCrossRefGoogle Scholar
  5. 5.
    E.S. Canellakis, D.A. Kyriakidis, C.A. Rinehart Jr., S.C. Huang, C. Panagiotidis and W.F. Fong, Regulation of polyamine biosynthesis by antizyme and some recent development relating the induction of polyamine biosynthesis to cell growth, Bioscience Reports, 5: 189 (1985).PubMedCrossRefGoogle Scholar
  6. 6.
    J.L.A. Mitchell, P. Qasba, R.E. Stofko and M.A. Fransen, Ornithine decarboxylase modification and polyamine-stimulated enzyme inactivation in HTC cells, Biochem.J., 228: 297 (1985).PubMedGoogle Scholar
  7. 7.
    F. Flamigni, C. Guarnieri, C. Stefanelli, F. Meggio, L.A. Pinna and C.M. Caldarera, Ornithine decarboxylase in the early phase of cardiac hypertrophy induced by isoproterenol, in: “Recent Progress in Polyamine Research”, L. Selmeci, M.E. Brosnan, N. Seiler, eds., Akademiai Kiado’, Budapest (1985).Google Scholar
  8. 8.
    F. Meggio, F. Flamigni, C.M. Caldarera, C. Guarnieri and L.A. Pinna, Phosphorylation of rat heart ornithine decarboxylase by type-2 casein kinase, Biochem.Biophys.Res. Commun, 122: 997 (1984).PubMedCrossRefGoogle Scholar
  9. 9.
    M.M. Bradford, A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding, Anal.Biochem., 72: 248 (1976).PubMedCrossRefGoogle Scholar
  10. 10.
    G.M. Hathaway and J.A. Traugh, Casein Kinase II, Meth.Enzymol, 99: 317 (1983).PubMedCrossRefGoogle Scholar
  11. 11.
    C. Cochet, G. Job, F. Pirollet and E.M. Chambaz, Cyclic nucleotide independent casein kinase (G type) in bovine adrenal cortex, Biochim. Biophys. Acta, 658: 191 (1981)PubMedGoogle Scholar
  12. 12.
    H.R. Schneider, G.H. Reichert and O.G. Issinger, Enhanced casein kinase II activity during mouse embryogenesis, Eur.J.Biochem., 161: 733 (1986).PubMedCrossRefGoogle Scholar
  13. 13.
    K. Prowald, H. Fisher and O.G. Issinger, Enhanced casein kinase II activity in human tumour cell cultures, FEBS Lett., 176: 479 (1984).PubMedCrossRefGoogle Scholar
  14. 14.
    A.M. Brunati, D. Soggioro, L. Chieco-Bianchi and L.A. Pinna, Altered protein kinase activities of lymphoid cells transformed by Abelson and Moloney Leukemia viruses, FEBS Lett., 206: 59 (1986).PubMedCrossRefGoogle Scholar
  15. 15.
    J. Sommercorn, J.A. Mulligan, F.J. Lozeman and E.G. Krebs, Activation of casein kinase II in responce to insulin and to epidermal growth factor, Proc. Natl. Acad. Sci USA, 84: 8834 (1987).PubMedCrossRefGoogle Scholar
  16. 16.
    P. Ackerman, V.C. Glover and N. Osheroff, Phosphorylation of DNA topoisomerase II by casein kinase II: modulation of eukaryotic topoisomerase II activity in vitro, Proc.Natl. Acad. Sci USA, 82: 3164 (1985).PubMedCrossRefGoogle Scholar
  17. 17.
    U.R. Tipnis and M.K. Haddox, Casein kinase II mediated phosphorylation of ornithine decarboxylase, J.Cell.Biol., 101: 356a (1985).Google Scholar
  18. 18.
    N.J. Donato, C.F. Ware and C.V. Byus, A rat monoclonal antibody which interacts with mammalian ornithine decarboxylase at an epitope involved in phosphorylation, Biochim.Biophys.Acta, 884: 370 (1986).PubMedCrossRefGoogle Scholar
  19. 19.
    C. Kahana and D. Nathans, Nucleotide sequence of murine ornithine decarboxylase in RNA, Proc.Natl.Acad.Sci. USA, 82: 1673 (1985).PubMedCrossRefGoogle Scholar
  20. 20.
    F. Meggio, A.M. Brunati and L.A. Pinna, Autophosphorylation of type 2 casein kinase TS at both its α-and β-subunits. Influence of different effectors, FEBS Lett., 160: 203 (1983)PubMedCrossRefGoogle Scholar
  21. 21.
    L.A. Pinna, P. Agostinis and S. Ferrari, Selectivity of protein kinases and protein phosphatases: a comparative analysis, Adv. Prot. Phosphatases, III: 327 (1986).Google Scholar
  22. 22.
    H.J. Van Kranen, L. Van de Zande, C.F. Van Kreijl, A. Bishop and B. Wieringa, Cloning and nucleotide sequence of rat ornithine decarboxylase cDNA, Gene, 60: 145 (1987).PubMedCrossRefGoogle Scholar
  23. 23.
    F. Meggio, F. Flamigni, C. Guarnieri and L.A. Pinna, Location of the phosphorylation site for casein kinase-2 within the aminoacid sequence of ornithine decarboxylase, Biochim. Biophys.Acta, 929: 114 (1987).PubMedCrossRefGoogle Scholar
  24. 24.
    M. Gupta and P. Coffino, Mouse ornithine decarboxylase.Complete aminoacid sequence deduced from cDNA, J. Bio1. Chem., 260: 2941 (1985).Google Scholar
  25. 25.
    N.J. Hickock, P.J. Seppanen, G.L. Gunsalus and O.A. Janne, Complete aminoacid sequence of human ornithine decarboxylase deduced from complementary DNA, DNA, 6: 179 (1987).CrossRefGoogle Scholar
  26. 26.
    P.R. Srinivasan, P.N. Tonin, E.J. Wensing and W.H. Lewis, The gene for ornithine decarboxylase is co-amplified in hydroxyurea-resistant hamster ceIls, J.Cell.Bio1., 262: 1287 (1987).Google Scholar
  27. 27.
    M.A. Phillips, P. Coffino and C.C. Wang, Cloning and sequencing of the ornithine decarboxylase gene from Trypanosomabrucei. Implications for enzyme turnover and selective difluoromethylornithine inhibition. J. Biol. Chem., 262: 8721 (1987).PubMedGoogle Scholar
  28. 28.
    S. Rogers, R. Weils and M. Rechsteiner, Aminoacid sequences common to rapidly degraded proteins: the PEST hypothesis, Science, 234: 364 (1986).PubMedCrossRefGoogle Scholar
  29. 29.
    C. Cochet, J.J. Feige, F. Pinollet, M. Keramidis and E.M. Chambaz, Selective inhibition of a cyclic nucleotide independent protein kinase (G type casein kinase) by quercetin and related polyphenols, Biochem.Pharmacol., 31: 1357 (1982).PubMedCrossRefGoogle Scholar
  30. 30.
    Y. Graziani and R. Chayoth, Regulation of cyclic AMP level and synthesis of DNA, RNA and protein by quercetin in Enrich ascites tumor cells, Biochem.Pharmacol, 28: 397 (1979).PubMedCrossRefGoogle Scholar
  31. 31.
    J. Janne and H.G. Williams-Ashman, On the purification of L-Or-nithine decarboxylase from rat prostate and effects of thiol compounds on the enzyme, J. Biol.Chem, 246: 1725 (1971)PubMedGoogle Scholar
  32. 32.
    M.F. Zuretti and E. Gravela, Studies on the mechanisms of ornithine decarboxylase in vitro inactivation, Biochim. Biophys.Acta, 742: 269 (1983).PubMedCrossRefGoogle Scholar
  33. 33.
    C. Danzin and L. Persson, L-ornithine-induced inactivation of mammalian ornithine decarboxylase in vitro, Eur. J. Biochem., 166: 45 (1987).PubMedCrossRefGoogle Scholar
  34. 34.
    C. Guarnieri, A. Lugaresi, F. Flamigni, C. Muscari and C.M. Caldarera, Effect of oxygen radicals and hyperoxia on rat heart ornithine decarboxylase activity, Biochim.Biophys. Acta, 718: 157 (1982).PubMedCrossRefGoogle Scholar
  35. 35.
    Y. Murakami, T. Kameji, S. Hayashi, Cysteine-dependent inactivation of hepatic ornithine decarboxylase, Biochem.J., 217: 573 (1984).PubMedGoogle Scholar
  36. 36.
    J.L.A. Mitchell, Post-translational controls of ornithine decarboxylase activity, Adv.Polyamine Res., 3: 15 (1981).Google Scholar
  37. 37.
    F. Flamigni, C. Guarnieri and C.M. Caldarera, Rat liver cytosol contains NADPH-and GSH-dependent factors able to restore ornithine decarboxylase inactivated by removal of thiol reducing agents, Biochem.J., 250: 53 (1988).PubMedGoogle Scholar
  38. 38.
    F. Flamigni, S. Marmiroli, C.M. Caldarera and C. Guarnieri, Involvement of thiol transferase and thioredoxin-dependent systems in the protection of “essential” thiol groups of ornithine decarboxylase, (submitted for publication).Google Scholar
  39. 39.
    K. Axelsson, S. Eriksson and B. Mannervik, Purification and characterization of cytoplasmic thiol transferase (Glutathione: disulfide oxidoreductase) from rat liver, Biochemistry, 17: 2978 (1978).PubMedCrossRefGoogle Scholar
  40. 40.
    A. Holmgren, Thioredoxin, Ann.Rev.Biochem., 54: 237 (1985).PubMedCrossRefGoogle Scholar
  41. 41.
    D.M. Ziegler, Role of reversible oxidation-reduction of enzyme thiols-disulfides in metabolic regulation. Ann. Rev. Biochem., 54: 305 (1985).PubMedCrossRefGoogle Scholar
  42. 42.
    C.E. Olson, A.H. Soll and N. Kaplowitz, Modulating effect of thiol-disulfide status on 14C aminopyrine accumulation in the isolated parietal cell, J.Biol.Chem., 260: 8020 (1985).PubMedGoogle Scholar
  43. 43.
    K. Sato, H. Mimura, K. Wakai, N. Tomari, T. Tsushiwa and K. Shizume, Modulating effect of glutathione disulfide on thyroxine-5′-deiodination by rat hepatocytes in primary culture: effect of glucose, Endocrinology, 113: 878 (1983).PubMedCrossRefGoogle Scholar
  44. 44.
    W.T. Beck, Increase by vinblastine of oxidized glutathione in cultured mammalian cells, Biochem.Pharmacol., 29: 2333 (1980).PubMedCrossRefGoogle Scholar
  45. 45.
    K.U. Shallreuter and J.M. Wood, Azelaic acid as a competitive inhibitor of thioredoxin reductase in human melanoma cells. Cancer Lett., 36: 297 (1987).CrossRefGoogle Scholar
  46. 46.
    F.C. Knowles and A.A. Benson, The biochemistry of arsenic, Trends Biochem.Sci., 9: 178 (1983).CrossRefGoogle Scholar
  47. 47.
    E. Karvonen, L.C. Andersson and H. Poso, A human neuroblastoma cell line with a stable ornithine decarboxylase in vivo and in vitro, Biochem. Biophys. Res. Commun., 126: 96 (1985).PubMedCrossRefGoogle Scholar
  48. 48.
    M.F. Zuretti, O. Brossa, P. Gili and E. Gravela, Ornithine decarboxylase properties: is there a role for a microsome-bound inactivating activity, Cell. Biochem. Funct., 6: 107 (1988).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Flavio Flamigni
    • 1
  • Flavio Meggio
    • 1
    • 2
  • Sandra Marmiroli
    • 1
  • Carlo Guarnieri
    • 1
  • Lorenzo A. Pinna
    • 1
    • 2
  • Claudio M. Caldarera
    • 1
  1. 1.Dipartimento di BiochimicaUniversity of BolognaItaly
  2. 2.Dipartimento di Chimica BiologicaUniversity of PadovaItaly

Personalised recommendations