Abstract
Altered protein glycosylation is known to correlate with tumorigenesis, but its role remains enigmatic. Cells transformed by altered oncogene or twnor suppressor gene expression often also show changes of carbohydrate on cell surface glycoconjugates which correlate with the potential for twnor invasion and metastasis. In recent years, many oncogene and twnor suppressor gene products, such as c-Myc, SV40 large T antigen, and p53, were shown to be modified by O-G1cNAc. O-G1cNAc is a form of protein glycosylation found almost exclusively in the nucleus and cytoplasm of eukaryotic cells. The known O-G1cNAc-bearing proteins are phosphoproteins and form reversible multimeric complexes. O-G1cNAc modification is dynamic and appears to have a reciprocal relationship with protein phosphorylation.
The enzymes which catalyze O-G1cNAc addition and removal have been characterized and used as effective tools in O-G1cNAc studies. It is of great interest in the future to investigate the alteration of O-G1cNAc in different cancers since addition/removal of 0-G1cNAc on oncoproteins, tumor suppressor proteins, and other tumor-related proteins very likely plays a key role in the pathogenesis of tumors.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Axford, J. Glycobiology and medicine: an introduction, Journal of the Royal Society of Medicine. 90: 260–264, 1997.
Hebert, E. and Monsigny, M. Oncogenes and expression of endogenous lectins and glycoconjugates, Biol. Cell. 79: 97–109, 1993.
Jiang, M. S., Passaniti, A., Penno, M. B., and Hart, G. W. Adrenal carcinoma tumor progression and penultimate cell surface oligosaccharides, Cancer Research. 52: 2222–2227, 1992.
Reese, M. R. and Chow, D. A. Tumor progression in vivo: Increased soybean agglutinin lectin binding, N-acetylgalactosamine-specific lectin expression, and liver metastasis potential, Cancer Research. 52: 5235–5243, 1992.
Bishop, J. M. Molecular Themes In Oncogenesis, Cell. 64: 235–248, 1991.
Hiraizumi, S., Takakasaki, S., Shiroki, K., and Kobata, A. Altered protein glycosylation of rat 3Y1 cells induced by activated c-myc gene, International Jounal of Cancer. 48: 305–310, 1991.
Dennis, J., Granovsky, M., and Warren, C. Glycoprotein glycosylation and cancer progression, Biochimica et Biophysica Acta - General Subjects. 1473: 21–34, 1999.
Muramatsu, T. Essential roles of carbohydrate signals in development, immune response and tissue functions, as revealed by gene targeting, Journal of Biochemistry. 127: 171–176, 2000.
Chou, T.-Y., Dang, C. V., and Hart, G. W., Glycosylation of the c-Myc transactivation domain, Proc. Natl. Acad. Sci. USA. 92: 4417–4421, 1995.
Chou, T. Y., Hart, G. W., and Dang, C. V. c-Myc Is Glycosylated at Threonine 58, a Known Phosphorylation Site and a Mutational Hot Spot in Lymphomas, J. Biol. Chem. 270: 18961–18965, 1995.
Shaw, P., Freeman, J., Bovey, R., and Iggo, R. Regulation of specific DNA binding by p53: evidence for a role for 0-glycosylation and charged residues at the carboxy-terminus, Oncogene. 12: 921–930, 1996.
Hart, G. W., Kreppel, L. K., Comer, F. I., Arnold, C. S., Snow, D. M., Ye, Z., Cheng, X., DellaManna, D., Caine, D. S., Earles, B. J., Akimoto, Y., Cole, R. N., and Hayes, B. K.OG1cNAcylation of key nuclear and cytoskeletal proteins: reciprocity with 0-phosphorylation and putative roles in protein multimerization, Glycobiology. 6: 711–716, 1996.
Hart, G. W. Dynamic 0-linked glycosylation of nuclear and cytoskeletal proteins, Annual Review of Biochemistry. 66: 315–335, 1997.
Snow, D. and Hart, G. Nuclear and cytoplasmic glycosylation, International Review of Cytology. 181: 43–74, 1998.
Schmidt-Ullrich, R., Thompson, W., and Wallach, D. Biochemical and immunochemical characterization of two simian virus 40 (SV40)-specific glycoproteins in nuclear and surface membranes of SV40-transformed cells, Biochem. Biophys. Res. Commun. 88: 887–894, 1979.
Schmidt-Ullrich, R., Thompson, W., Kahn, S., Monroe, M., and Wallach, D. Simian virus 40 (SV40)-specific isoelectric point-4.7–94,000-Mr membrane glycoprotein: membrane-associated 94,000-Mr SV40 T-antigen in hamsters, J. Natl. Cancer Inst. 69: 839–849, 1982.
Privalsky, M. A subpopulation of the avian erythroblastosis virus v-erbA protein, a member of the nuclear hormone receptor family, is glycosylated, Journal of Virology. 64: 463–466, 1990.
Ryan, K. M. and Birnie, G. D. Myc oncogenes: the enigmatic family, Biochemical Journal. 314: 713–721, 1996.
Henriksson, M. and Luscher, B. Proteins of the Myc network: essential regulators of cell growth and differentiation, Advances in Cancer Research. 68: 109–182, 1996.
Lutterbach, B. and Hann, S. R. Hierarchical phosphorylation at N-terminal transformation-sensitive sites in c-Myc protein is regulated by mitogens and in mitosis, Mol. Cell. Biol. 14: 5510–5522,1994.
Henriksson, M., Bakardjiev, A., Klein, G., and Luscher, B. Phosphorylation sites mapping in the N-terminal domain of c-Myc modulate its transforming potential, Oncogene. 8: 3199–3209, 1993.
Frykberg, L., Graf, T., and Vennstrom, B. The transforming activity of the chicken c-myc gene can be potentiated by mutations, Oncogene. 1: 415–421, 1987.
Raffeld, M., Yano, T., Hoang, A. T., Lewis, B., Clark, H. M., Otsuki, T., and Dang, C. V. Clustered Mutations in the Transcriptional Activation Domain of Myc in 8q24 Translocated lymphomas and Their Functional Consequences, Curr. Top. Microbiol. Immunol. 194: 265–272, 1995.
Medina, L., Grove, K., and Haltiwanger, R. SV40 large T antigen is modified with 0-linked N-acetylglucosamine but not with other forms of glycosylation, Glycobiology. 8: 383–391, 1998.
Hayes, B. and Hart, G. Protein O-G1cNAcylation: potential mechanisms for the regulation of protein function. In: Axford (ed.) Glycoimmunology 2, pp. 85–94. New York: Plenum Press, 1998.
Kreppel, L. K., Blomberg, M. A., and Hert, G. W. Dynamic glycosylation of nuclear and cytosolic proteins. Cloning and characterization of a unique O-GlcNAc transferase with multiple tetratricopepdite repeats, The Journal of Biological Chemistry. 272: 9308–9315, 1997.
Lubas, W. A., Frank, D. W., Krause, M., and Hanover, J. A. 0-linked GlcNAc transferase is a conserved nucleocytoplasmic protein containing tetratricopeptide repeats, The Journal of Biologiaal Chemistry. 272: 9316–9324, 1997.
Hanover, J., Lai, Z., Lee, G., Lubas, W., and Sato, S. Elevated 0-linked N-acetylglucosamine metabolism in pancreatic beta-cells, Archives of Biochemistry and Biophysics. 362: 38–45, 1998.
Akimoto, Y., Kreppel, L., Hirano, H., and Hart, G. Localization of the 0-linkedNacetylglucosamine transferase in rat pancreas, Diabetes. 48: 2407–2413, 1999.
Kreppel, L. and Hart, G. Regulation of a cytosolic and nuclear O-G1cNAc transferase: role of the tetratricopeptide repeats, The Journal of Biological Chemistry. 274: 32015–32022, 1999.
Lubas, W. and Hanover, J. Functional expression of 0-linked GlcNAc transferase - Domain structure and substrate specificity, The Journal of Biological Chemistry. 275: 10983–10988, 2000.
Dong, D. L.-Y. and Hart, G. W. Purification and characterization of an O-G1cNAc selectiveNAcetyl-B-D-glucosaminidasefrom rat spleen cytosol, The Journal of Biological Chemistry. 269: 19321–19330, 1994.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2001 Springer Science+Business Media New York
About this chapter
Cite this chapter
Chou, TY., Hart, G.W. (2001). O-Linked N-Acetylglucosamine and Cancer: Messages from the Glycosylation of C-Myc. In: Wu, A.M. (eds) The Molecular Immunology of Complex Carbohydrates —2. Advances in Experimental Medicine and Biology, vol 491. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1267-7_26
Download citation
DOI: https://doi.org/10.1007/978-1-4615-1267-7_26
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-5469-7
Online ISBN: 978-1-4615-1267-7
eBook Packages: Springer Book Archive