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Protein O-GlcNAcylation: Potential Mechanisms for the Regulation of Protein Function

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Glycoimmunology 2

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 435))

Abstract

Protein O-GlcNAcylation is the process whereby single N-acetylglucosamine residues are glycosidically linked to the hydroxyl side chains of specific serine and threonine residues. O-GlcNAc was originally identified while probing the surfaces of lymphocytes using UDP-[3H] galactose and highly purified galactosyltransferase (1). O-GlcNAc was not a substrate for galactosyltransferase unless the cell membrane was first disrupted with detergents indicating that it is an intracellular glycosylation. Subcellular fractionation further demonstrated that O-GlcNAc is found exclusively on nuclear and cytosolic proteins (2,3). Galactosyltransferase labeling of mouse liver nuclei with subsequent analysis by 2-dimensional gel electrophoresis and fluorography indicates that a large number of nuclear proteins are modified with O-GlcNAc residues and suggests that O-GlcNAc is as abundant as phosphorylation (4).

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References

  1. C.-R. Torres, and G.W. Hart, Topography and polypeptide distribution of terminal N-acetylglucosamine residues on the surfaces of intact lymphocytes. J. Biol. Chem. 259:3308 (1984).

    PubMed  CAS  Google Scholar 

  2. G. D. Holt, and G. W. Hart, The subcellular distribution of terminal N-acetylglucosamine moieties. Localization of a novel protein-saccharide linkage, O-linked GlcNAc, J. Biol Chem. 261:8049 (1986).

    PubMed  CAS  Google Scholar 

  3. K. P. Kearse, and G. W. Hart, Topology of O-linked N-acetylglucosamine in murine lymphocytes, Arch. Biochem. Biophys. 290:543 (1991).

    Article  PubMed  CAS  Google Scholar 

  4. G. W. Hart, K. D. Greis, D. L.-Y. Dong, M. A. Blomberg, T.-Y. Chou, M.-S. Jaing, E. P. Roquemore, D. M. Snow, L. K. Kreppel, R. N. Cole, and B. K. Hayes, Ubiquitous and temporal glycosylation of nuclear and cytoplasmic proteins, Pure and Appl. Chem. 67:1637 (1995).

    Article  CAS  Google Scholar 

  5. M. Machida, and Y. Jigami, Glycosylated DNA-binding proteins from filamentous fungus, Aspergillus orzyae: modification with N-acetylglucosamine monosaccharide through an O-glycosidic linkage Biosci. Biotech. Biochem. 58:344 (1994).

    Article  CAS  Google Scholar 

  6. E. Ortega-Barria, H. D. Ward, J. E. Evans, and M. E. A. Pereira, N-acetylglucosamine is present in cysts and trophozoites of Giardia lamblia and serves as receptor for wheat germ agglutinin, Mol. Biochem. Parasitol. 43:151 (1990).

    Article  PubMed  CAS  Google Scholar 

  7. A. Dieckmann-Schuppert, E. Bause, and R. T. Schwarz, Studies on O-glycans of Plasmodium falciparum-infected human erythrocytes: evidence for O-GlcNAc and O-GlcNAc transferase in malaria parasites, Eur. J. Biochem. 216:779 (1993).

    Article  PubMed  CAS  Google Scholar 

  8. J. O. Previato, C. Jones, L. P. B. Goncalves, R. Wait, L. R. Travassos, and L. Mendonca-Previato, O-Glycosidically linked N-acetylglucosamine-bound oligosaccharides from glycoproteins of Trypanosoma cruzi, Biochem. J. 301:151 (1994).

    PubMed  CAS  Google Scholar 

  9. S. A. Gonzalez, and O. R. Burrone, Rotavirus NS26 is modified by addition of single O-linked residues of N-acetylglucosamine, Virology 182:8 (1992).

    Article  Google Scholar 

  10. K. D. Greis, W. Gibson, and G. W. Hart, Site-specific glycosylation of the human cytomegalovirus tegument basic phosphoprotein (UL32) at serine 921 and serine 952, J. Virol 68:8339 (1994).

    PubMed  CAS  Google Scholar 

  11. M. Whitford, and P. Faulkner, A structural polypeptide of the baculovirus Autographa californica nuclear polyhedris virus contains O-linked N-acetylglucosamine, J. Virol 66:3324 (1992).

    PubMed  CAS  Google Scholar 

  12. K. G. Mullis, R. S. Haitiwanger, G. W. Hart, R. B. Marchase, and J. A. Engler, Relative accessibility of N-acetylglucosamine in trimers of the Adenovirus types 2 and 5 fiber proteins J. Virol 64:5317 (1990).

    PubMed  CAS  Google Scholar 

  13. L. Medina-Vera, and R. S. Haltiwanger, SV-40 Large T antigen is modified with O-linked N-acetylglucosamine, Mol Biol Cell 5(S):340a (1994).

    Google Scholar 

  14. G. W. Hart, Dynamic O-GlcNAcylation of nuclear and cytoskeletal proteins, Ann. Rev. Biochem. In Press (1997).

    Google Scholar 

  15. S. P. Jackson, and R. Tjian, O-Glycosylation of eukaryotic transcription factors: implications for mechanisms of transcriptional regulation, Cell 55:125 (1988).

    Article  PubMed  CAS  Google Scholar 

  16. A. J. Reason, H. R. Morris, M. Panico, R. Marais, R. H. Treisman, R. S. Haltiwanger, G. W. Hart, W. G. Kelly, and A. Dell, Localization of O-GlcNAc modification on the serum response transcription factor, J. Biol Chem. 267:16911 (1992).

    PubMed  CAS  Google Scholar 

  17. M.-S. Jiang and G. W. Hart, A subpopulation of estrogen receptors are modified by O-linked N-acetylglucosamine, J. Biol Chem. In Press (1997).

    Google Scholar 

  18. S. Murphy, A. Pierani, C. Scheidereit, M. Melli, and R. G. Roeder, Purified octamer binding transcription factors stimulate RNA polymerase III-mediated transcription of the 7SK RNA gene, Cell 59:1071 (1989).

    Article  PubMed  CAS  Google Scholar 

  19. S. Lichtsteiner, and U. Schibler, A Glycosylated liver-specific transcription factor stimulates transcription of the albumin gene, Cell 57:1179 (1989).

    Article  PubMed  CAS  Google Scholar 

  20. F. P. Lemaigre, S. M. Durviaux, O. Truong, V. J. Lannoy, J. J. Hsuan, and G. G. Rousseau, Hepatocyte nuclear factor 6, a transcription factor that contains a novel type of homeodomain and single cut domain, Proc. Natl. Academ. Sci U. S. A. 93:9460 (1996).

    Article  CAS  Google Scholar 

  21. T.-Y. Chou, C. V. Dang, and G. W. Hart, Glycosylation of c-Myc transactivation domain, Proc. Natl. Academ. Sci U. S. A. 92:4417 (1995).

    Article  CAS  Google Scholar 

  22. M. L. Privalsky, A subpopulation of the avian Erythroblastosis virus v-erbA protein, a member of the nuclear hormone receptor family, is glycosylated, J. Virol. 64:463 (1990).

    PubMed  CAS  Google Scholar 

  23. P. Shaw, J. Freeman, R. Bovey, and R. Iggo, Regulation of specific DNA binding by p53: evidence for a role for O-glycosylation and charged residues at the carboxy terminus, Oncogene 12:921 (1996).

    PubMed  CAS  Google Scholar 

  24. C.-F. Chou, A. J. Smith, and M. B. Omary, Characterization and dynamics of O-linked glycosylation of human cytokeratins 8 and 18, J. Biol. Chem. 267:3901 (1992).

    PubMed  CAS  Google Scholar 

  25. I. A. King, and E. F. Hounsell, Cytokeratin 13 contains O-glycosidically linked N-acetylglucosamine, J. Biol Chem. 264:14022 (1989).

    PubMed  CAS  Google Scholar 

  26. D. L.-Y. Dong, Z.-S. Xu, M. R. Chevrier, R. J. Cotter, D. W. Cleveland, and G. W. Hart, Glycosylation of mammalian neurofilaments: localization of multiple O-linked N-acetylglucosamine moieties on neurofilament polypeptides L and M, J. Biol. Chem. 268:16679 (1993).

    PubMed  CAS  Google Scholar 

  27. D. L.-Y. Dong, Z.-S. Xu, G. W. Hart, and D. W. Cleveland, Cytoplasmic O-GlcNAc modification of the head domain and the KSP repeat motif of the neuofilament protein neurofilament H, J. Biol. Chem. 271:20845 (1996).

    Article  PubMed  CAS  Google Scholar 

  28. C. S. Arnold, G. V. W. Johnson, R. N. Cole, D. L.-Y. Dong, M. Lee, and G. W. Hart, The microtubule-associated protein Tau is extensively modified with O-linked N-acetylglucosamine, J. Biol. Chem. 271:28741 (1996).

    Article  PubMed  CAS  Google Scholar 

  29. M. Ding, and D. D. Vandre, High molecular weight microtubule-associated proteins contain O-linked N-acetylglucosamine, J. Biol Chem. 271:12555 (1996).

    Article  PubMed  CAS  Google Scholar 

  30. M. Inaba, and Y. Meade, O-N-Acetyl-D-glueosamine moiety on discrete peptide of multiple Protein 4.1 isoforms regulated by alternative pathways, J. Biol. Chem. 264:18149 (1989).

    PubMed  CAS  Google Scholar 

  31. J. Hagmann, M. Grob, and M. M. Burger, The cytoskeletal protein Talin is O-glycosylated, J. Biol Chem. 267:14424 (1992).

    PubMed  CAS  Google Scholar 

  32. J. G. Vostal, and D. M. Krasnewich, Dynamic O-linked N-acetylglucosamine glycosylation of platelet vinculin, Mol. Biol. Cell 5(S):263a (1994).

    Google Scholar 

  33. T. Luthi, R. S. Haltiwanger, P. Greengard, and M. Bahler, Synapsins contain O-linked N-acetylglucosamine, J. Neurochem. 56:1493 (1991).

    Article  PubMed  CAS  Google Scholar 

  34. X. Zhang, and V. Bennett, Identification of O-linked N-acetylglucosamine modification of AnkyrinG isoforms targeted to Nodes of Ranvier, J. Biol Chem. 271:31391 (1996).

    Article  PubMed  CAS  Google Scholar 

  35. W. Meikrantz, D. M. Smith, M. M. Sladicka, and R. A. Schlegel, Nuclear localization of an O-glycosylated protein phosphotyrosine phosphatase from human cells, J. Cell Sci. 98:303 (1991).

    PubMed  CAS  Google Scholar 

  36. T. Matsuoka, G. V. W. Johnson and G. W. Hart, In Preparation.

    Google Scholar 

  37. W. G. Kelly, M. E. Dahmus, and G. W. Hart, RNA polymerase II is a glycoprotein: modification of the COOH-terminal domain by O-GlcNAc, J. Biol Chem. 268:10416 (1993).

    PubMed  CAS  Google Scholar 

  38. L. S. Griffith, M. Mathes, and B. Schmitz, β-Amyloid precursor protein is modified with O-linked N-acetylglucosamine, J. Neurosci. Res. 41:270 (1995).

    Article  PubMed  CAS  Google Scholar 

  39. C. Abeijon, and C. B. Hirschberg, Intrinsic membrane glycoproteins with cytosol-oriented sugars in the endoplasmic reticulum, Proc. Natl Academ. Sci. U. S. A. 85:1010 (1988).

    Article  CAS  Google Scholar 

  40. J. M. Capasso, C. Abeijon, and c. B. Hirschberg, An intrinsic membrane glycoprotein of the Golgi apparatus with O-linked N-acetylglucosamine facing the cytosol, J. Biol Chem 263:19778 (1988).

    PubMed  CAS  Google Scholar 

  41. B. K. Hayes, and G. W. Hart, In search of O-GlcNAcylated proteins, Glycobiology 6:737 (1996).

    Google Scholar 

  42. B. K. Hayes, K. D. Greis, and G. W. Hart, Specific isolation of O-linked N-acetylglucosamine glycopeptides from complex mixtures, Anal Biochem. 228:115 (1995).

    Article  PubMed  CAS  Google Scholar 

  43. K. D. Greis, B. K. Hayes, F. I. Comer, M. Kirk, S. Barnes, T. L. Lowary, and G. W. Hart, Selective detection and site-analysis of O-GlcNAc-modified glycopeptides by β-elimination and tandem electrospray mass spectrometry, Anal. Biochem. 234:38 (1996).

    Article  PubMed  CAS  Google Scholar 

  44. R. S. Haltiwanger, M. A. Blomberg, and G. W. Hart, Glycosylation of nuclear and cytoplasmic proteins: purification and characterization of a UDP-GlcNAc:polypeptide β-N-Acetylglucosaminyltransferase, J. Biol Chem. 267:9005 (1992).

    PubMed  CAS  Google Scholar 

  45. D. L.-Y. Dong, and G. W. Hart, Purification and characterization of an O-GlcNAc selective N-Acetyl-β-D-glucosaminidase from rat spleen cytosol, J. Biol Chem. 269:19321 (1994).

    PubMed  CAS  Google Scholar 

  46. E. P. Roquemore, M. R. Chevrier, R. J. Cotter, and G. W. Hart, Dynamic O-GlcNAcylation of the small heat shock protein αB-crystallin, Biochemistry 35:3578 (1996).

    Article  PubMed  CAS  Google Scholar 

  47. C.-F. Chou, and M. B. Omary, Mitotic arrest-associated enhancement of O-linked glycosylation and phosphorylation of human keratins 8 and 18, J. Biol Chem. 268:4465 (1993).

    PubMed  CAS  Google Scholar 

  48. K. P. Kearse, and G. W. Hart, Lymphocyte activation induces rapid changes in nuclear and cytoplasmic glycoproteins, Proc. Natl. Academ. Sci. U. S. A. 88:1701 (1991).

    Article  CAS  Google Scholar 

  49. T.-Y. Chou, G. W. Hart, and C. V. Dang, c-Myc is glycosylated at threonine 58, a known phosphorylation site and a mutational hot spot in lymphomas, J. Biol. Chem. 270:18961 (1995).

    Article  PubMed  CAS  Google Scholar 

  50. E. M. Mandelkow, O. Schweers, G. Dewes, J. Biernat, N. Gustke, B. Trinczek, and E. Mandelkow, Structure, microtubule interactions, and phosphorylation of the Tau protein, Annals N. Y. Academ Sci. 777:96 (1996).

    Article  CAS  Google Scholar 

  51. J. Selzer, F. Hofmann, G. Rex, M. Wilm, M. Mann, I. Just, and K. Aktories, Clostridium novyi α-toxin-catalyzed incorporation of GlcNAc into Rho subfamily proteins, J. Biol Chem. 271:25173 (1996).

    Article  PubMed  CAS  Google Scholar 

  52. C. M. Starr, and J. A. Hanover, Glycosylation of nuclear pore protein p62. reticulocyte lysate catalyzes O-linked N-acetylglucosamine addition in vitro, J. Biol. Chem. 265:6868 (1990).

    PubMed  CAS  Google Scholar 

  53. G. Fisher, and F. X. Schmid, The mechanism of protein folding: Implications of in vitro refolding models for de novo protein folding and translocation in the cell, Biochemistry 29:2205 (1990).

    Article  Google Scholar 

  54. Y.-L. Pan, M. R. Wormarld, R. A. Dwek, and A. C. Lellouch, Effect of serine O-glycosylation on cis-trans proline isomerization, Biochem. Biophys. Res. Commun. 219:157 (1996).

    Article  Google Scholar 

  55. N. Jentoft, Why are proteins O-glycosylated?, Trends Biochem. Sci. 15:291 (1990).

    Article  PubMed  CAS  Google Scholar 

  56. A. H. Andreotti, and D. Kahne, Effects of glycosylation on peptide backbone conformation, J. Amer. Chem. Soc. 115:3352 (1993).

    Article  CAS  Google Scholar 

  57. X. Liu, J. Sejbal, G. Kotovych, R. R. Koganty, M. A. Reddish, L. Jackson, S. S. Gandhi, A. J. Mendonca, and B. M. Longenecker, Structurally defined synthetic cancer vaccines: analysis of structure, glycosylation and recognition of cancer associated mucin, MUC-1 derived peptides, Glyconjugate J. 12:607 (1995).

    Article  CAS  Google Scholar 

  58. F. I. Comer, and G. W. Hart, Investigating the role of O-GlcNAc on RNA polymerase II, FASEB J. 10:A1119 (1996).

    Google Scholar 

  59. L. K. Kreppel, M. A. Blomberg, and G. W. Hart, Dynamic glycosylation of nuclear and cytosolic proteins: cloning and characterization of unique O-GlcNAc transferase with multiple tetratricopeptide repeats, J. Biol. Chem. In Press (1997).

    Google Scholar 

  60. J. R. Lamb, S. Tugendreich, and P. Hieter, Tetratricopeptide repeat interactions: to TPR or not to TPR? Trends Biochem. Sci. 20:257 (1995).

    Article  PubMed  CAS  Google Scholar 

  61. W. K. Gottschalk, J. Stuart, T. Wang, J. Weiel, and S. Marshall, Nuclear localization of a novel glycosyltransferase, FASEB J. 9:A1362 (1995).

    Google Scholar 

  62. S. E. Jackson, K. A. Binkowski, and N. E. Olszewski, SPINDLY, a tetratricopeptide repeat protein involved in gibberellin signal transduction in Arabidopsis, Proc. Natl. Academ. Sci. U. S. A. 93:9292 (1996).

    Article  Google Scholar 

  63. K. L. Bennett, B. Modrell, B. Greenfield, A. Bartolazzi, I. Stamenkovic, R. Peach, D. G. Jackson, F. Spring, and A. Aruffo, Regulation of CD44 binding to hyaluronan by glycosylation of variably spliced exons, J. Cell Biol. 131:1623 (1995).

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, 35294-0005, UK

    Bradley K. Hayes & Gerald W. Hart

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  1. Bradley K. Hayes
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  2. Gerald W. Hart
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  1. St. George’s Hospital Medical School, University of London, London, UK

    John S. Axford

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Hayes, B.K., Hart, G.W. (1998). Protein O-GlcNAcylation: Potential Mechanisms for the Regulation of Protein Function. In: Axford, J.S. (eds) Glycoimmunology 2. Advances in Experimental Medicine and Biology, vol 435. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5383-0_9

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  • DOI: https://doi.org/10.1007/978-1-4615-5383-0_9

  • Publisher Name: Springer, Boston, MA

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