Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Opinion
  • Published:

O-GlcNAc signalling: implications for cancer cell biology

Nature Reviews Cancer volume 11, pages 678–684 (2011)Cite this article

Subjects

Abstract

O-GlcNAcylation is the covalent attachment of β-D-N-acetylglucosamine (GlcNAc) sugars to serine or threonine residues of nuclear and cytoplasmic proteins, and it is involved in extensive crosstalk with other post-translational modifications, such as phosphorylation. O-GlcNAcylation is becoming increasing realized as having important roles in cancer-relevant processes, such as cell signalling, transcription, cell division, metabolism and cytoskeletal regulation. However, currently little is known about the specific roles of aberrant O-GlcNAcylation in cancer. In this Opinion article, we summarize the current understanding of O-GlcNAcylation in cancer and its emerging functions in transcriptional regulation at the level of chromatin and transcription factors.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: O-GlcNAc modifies the transcriptional machinery.
Figure 2: Histone O-GlcNAcylation increases after stress.
Figure 3: Regulation of transcription factors by O-GlcNAc.

Similar content being viewed by others

References

  1. Hart, G. W. & Copeland, R. J. Glycomics hits the big time. Cell 143, 672–676 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Torres, C. R. & Hart, G. W. Topography and polypeptide distribution of terminal N-acetylglucosamine residues on the surfaces of intact lymphocytes. Evidence for O-linked GlcNAc. J. Biol. Chem. 259, 3308–3317 (1984).

    Article  CAS  PubMed  Google Scholar 

  3. Hart, G. W., Housley, M. P. & Slawson, C. Cycling of O-linked β-N-acetylglucosamine on nucleocytoplasmic proteins. Nature 446, 1017–1022 (2007).

    Article  CAS  PubMed  Google Scholar 

  4. Carrillo, L. D., Froemming, J. A. & Mahal, L. K. Targeted in vivo O-GLcNAc sensors reveal discrete compartment-specific dynamics during signal transduction. J. Biol. Chem. 286, 6650–6658 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Hart, G. W., Slawson, C., Ramirez-Correa, G. & Lagerlof, O. Cross talk between O-GlcNAcylation and phosphorylation: roles in signaling, transcription, and chronic disease. Annu. Rev. Biochem. 80, 825–858 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Slawson, C., Copeland, R. J. & Hart, G. W. O-GlcNAc signaling: a metabolic link between diabetes and cancer? Trends Biochem. Sci. 35, 547–555 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Haltiwanger, R. S., Holt, G. D. & Hart, G. W. Enzymatic addition of O-GlcNAc to nuclear and cytoplasmic proteins. Identification of a uridine diphospho-N-acetylglucosamine:peptide β-N-acetylglucosaminyltransferase. J. Biol. Chem. 265, 2563–2568 (1990).

    Article  CAS  PubMed  Google Scholar 

  8. Dong, D. L. & Hart, G. W. Purification and characterization of an O-GlcNAc selective N-acetyl-β-D-glucosaminidase from rat spleen cytosol. J. Biol. Chem. 269, 19321–19330 (1994).

    Article  CAS  PubMed  Google Scholar 

  9. Slawson, C., Pidala, J. & Potter, R. Increased N-acetyl-β-glucosaminidase activity in primary breast carcinomas corresponds to a decrease in N-acetylglucosamine containing proteins. Biochim. Biophys. Acta 1537, 147–157 (2001).

    Article  CAS  PubMed  Google Scholar 

  10. Krzeslak, A., Pomorski, L. & Lipinska, A. Elevation of nucleocytoplasmic β-N-acetylglucosaminidase (O-GlcNAcase) activity in thyroid cancers. Int. J. Mol. Med. 25, 643–648 (2010).

    Article  CAS  PubMed  Google Scholar 

  11. Gu, Y. et al. GlcNAcylation plays an essential role in breast cancer metastasis. Cancer Res. 70, 6344–6351 (2010).

    Article  CAS  PubMed  Google Scholar 

  12. Mi, W. et al. O-GlcNAcylation is a novel regulator of lung and colon cancer malignancy. Biochim. Biophys. Acta 1812, 514–519 (2011).

    Article  CAS  PubMed  Google Scholar 

  13. Shi, Y. et al. Aberrant O-GlcNAcylation characterizes chronic lymphocytic leukemia. Leukemia 24, 1588–1598 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Slawson, C. et al. Perturbations in O-linked β-N-acetylglucosamine protein modification cause severe defects in mitotic progression and cytokinesis. J. Biol. Chem. 280, 32944–32956 (2005).

    Article  CAS  PubMed  Google Scholar 

  15. Love, D. C. et al. Dynamic O-GlcNAc cycling at promoters of Caenorhabditis elegans genes regulating longevity, stress, and immunity. Proc. Natl Acad. Sci. USA 107, 7413–7418 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Whisenhunt, T. R. et al. Disrupting the enzyme complex regulating O-GlcNAcylation blocks signaling and development. Glycobiology 16, 551–563 (2006).

    Article  CAS  PubMed  Google Scholar 

  17. Kazemi, Z., Chang, H., Haserodt, S., McKen, C. & Zachara, N. E. O-linked β-N-acetylglucosamine (O-GlcNAc) regulates stress-induced heat shock protein expression in a GSK-3β-dependent manner. J. Biol. Chem. 285, 39096–39107 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Caldwell, S. A. et al. Nutrient sensor O-GlcNAc transferase regulates breast cancer tumorigenesis through targeting of the oncogenic transcription factor FoxM1. Oncogene 29, 2831–2842 (2010).

    Article  CAS  PubMed  Google Scholar 

  19. Housley, M. P. et al. O-GlcNAc regulates FoxO activation in response to glucose. J. Biol. Chem. 283, 16283–16292 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Housley, M. P. et al. A PGC-1α-O-GlcNAc transferase complex regulates FoxO transcription factor activity in response to glucose. J. Biol. Chem. 284, 5148–5157 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ho, S. R. et al. O-GlcNAcylation enhances FOXO4 transcriptional regulation in response to stress. FEBS Lett. 584, 49–54 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ho, K. K., Myatt, S. S. & Lam, E. W. Many forks in the path: cycling with FoxO. Oncogene 27, 2300–2311 (2008).

    Article  CAS  PubMed  Google Scholar 

  23. Park, S. Y. et al. Snail1 is stabilized by O-GlcNAc modification in hyperglycaemic condition. EMBO J. 29, 3787–3796 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ingham, P. W. A gene that regulates the bithorax complex differentially in larval and adult cells of Drosophila. Cell 37, 815–823 (1984).

    Article  CAS  PubMed  Google Scholar 

  25. Sinclair, D. A. et al. Drosophila O-GlcNAc transferase (OGT) is encoded by the Polycomb group (PcG) gene, super sex combs (sxc). Proc. Natl Acad. Sci. USA 106, 13427–13432 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Gambetta, M. C., Oktaba, K. & Muller, J. Essential role of the glycosyltransferase sxc/Ogt in polycomb repression. Science 325, 93–96 (2009).

    Article  CAS  PubMed  Google Scholar 

  27. Mills, A. A. Throwing the cancer switch: reciprocal roles of polycomb and trithorax proteins. Nature Rev. Cancer 10, 669–682 (2010).

    Article  CAS  Google Scholar 

  28. Shah, N. & Sukumar, S. The Hox genes and their roles in oncogenesis. Nature Rev. Cancer 10, 361–371 (2010).

    Article  CAS  Google Scholar 

  29. Kelly, W. G. & Hart, G. W. Glycosylation of chromosomal proteins: localization of O-linked N-acetylglucosamine in Drosophila chromatin. Cell 57, 243–251 (1989).

    Article  CAS  PubMed  Google Scholar 

  30. Cao, R., Tsukada, Y. & Zhang, Y. Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. Mol. Cell 20, 845–854 (2005).

    Article  CAS  PubMed  Google Scholar 

  31. Berdasco, M. & Esteller, M. Aberrant epigenetic landscape in cancer: how cellular identity goes awry. Dev. Cell 19, 698–711 (2010).

    Article  CAS  PubMed  Google Scholar 

  32. Kelly, W. G., Dahmus, M. E. & Hart, G. W. RNA polymerase II is a glycoprotein. Modification of the COOH-terminal domain by O-GlcNAc. J. Biol. Chem. 268, 10416–10424 (1993).

    Article  CAS  PubMed  Google Scholar 

  33. Comer, F. I. & Hart, G. W. O-GlcNAc and the control of gene expression. Biochim. Biophys. Acta 1473, 161–171 (1999).

    Article  CAS  PubMed  Google Scholar 

  34. Comer, F. I. & Hart, G. W. Reciprocity between O-GlcNAc and O-phosphate on the carboxyl terminal domain of RNA polymerase II. Biochemistry 40, 7845–7852 (2001).

    Article  CAS  PubMed  Google Scholar 

  35. Yang, X., Zhang, F. & Kudlow, J. E. Recruitment of O-GlcNAc transferase to promoters by corepressor mSin3A: coupling protein O-GlcNAcylation to transcriptional repression. Cell 110, 69–80 (2002).

    Article  CAS  PubMed  Google Scholar 

  36. Cai, Y. et al. Subunit composition and substrate specificity of a MOF-containing histone acetyltransferase distinct from the male-specific lethal (MSL) complex. J. Biol. Chem. 285, 4268–4272 (2010).

    Article  CAS  PubMed  Google Scholar 

  37. Mendjan, S. et al. Nuclear pore components are involved in the transcriptional regulation of dosage compensation in Drosophila. Mol. Cell 21, 811–823 (2006).

    Article  CAS  PubMed  Google Scholar 

  38. Cheung, W. D., Sakabe, K., Housley, M. P., Dias, W. B. & Hart, G. W. O-linked β-N-acetylglucosaminyltransferase substrate specificity is regulated by myosin phosphatase targeting and other interacting proteins. J. Biol. Chem. 283, 33935–33941 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Sakabe, K. & Hart, G. W. O-GlcNAc transferase regulates mitotic chromatin dynamics. J. Biol. Chem. 285, 34460–34468 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Fujiki, R. et al. GlcNAcylation of a histone methyltransferase in retinoic-acid-induced granulopoiesis. Nature 459, 455–459 (2009).

    Article  CAS  PubMed  Google Scholar 

  41. Wang, Z., Pandey, A. & Hart, G. W. Dynamic interplay between O-linked N-acetylglucosaminylation and glycogen synthase kinase-3-dependent phosphorylation. Mol. Cell Proteomics 6, 1365–1379 (2007).

    Article  CAS  PubMed  Google Scholar 

  42. Wang, Z. et al. Extensive crosstalk between O-GlcNAcylation and phosphorylation regulates cytokinesis. Sci. Signal. 3, ra2 (2010).

    PubMed  PubMed Central  Google Scholar 

  43. Capotosti, F. et al. O-GlcNAc transferase catalyzes site-specific proteolysis of HCF-1. Cell 144, 376–388 (2011).

    Article  CAS  PubMed  Google Scholar 

  44. Daou, S. et al. Crosstalk between O-GlcNAcylation and proteolytic cleavage regulates the host cell factor-1 maturation pathway. Proc. Natl Acad. Sci. USA 108, 2747–2752 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Heit, R., Rattner, J. B., Chan, G. K. & Hendzel, M. J. G2 histone methylation is required for the proper segregation of chromosomes. J. Cell Sci. 122, 2957–2968 (2009).

    Article  CAS  PubMed  Google Scholar 

  46. Sakabe, K., Wang, Z. & Hart, G. W. β-N-acetylglucosamine (O-GlcNAc) is part of the histone code. Proc. Natl Acad. Sci. USA 107, 19915–19920 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Maile, T., Kwoczynski, S., Katzenberger, R. J., Wassarman, D. A. & Sauer, F. TAF1 activates transcription by phosphorylation of serine 33 in histone H2B. Science 304, 1010–1014 (2004).

    Article  CAS  PubMed  Google Scholar 

  48. Olson, L. E. et al. Homeodomain-mediated β-catenin-dependent switching events dictate cell-lineage determination. Cell 125, 593–605 (2006).

    Article  CAS  PubMed  Google Scholar 

  49. Mayya, V. et al. Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci. Signal. 2, ra46 (2009).

    Article  PubMed  Google Scholar 

  50. Perez-Cadahia, B., Drobic, B. & Davie, J. R. H3 phosphorylation: dual role in mitosis and interphase. Biochem. Cell Biol. 87, 695–709 (2009).

    Article  CAS  PubMed  Google Scholar 

  51. Wei, Y., Yu, L., Bowen, J., Gorovsky, M. A. & Allis, C. D. Phosphorylation of histone H3 is required for proper chromosome condensation and segregation. Cell 97, 99–109 (1999).

    Article  CAS  PubMed  Google Scholar 

  52. Mahadevan, L. C., Willis, A. C. & Barratt, M. J. Rapid histone H3 phosphorylation in response to growth factors, phorbol esters, okadaic acid, and protein synthesis inhibitors. Cell 65, 775–783 (1991).

    Article  CAS  PubMed  Google Scholar 

  53. Chen, Y. X. et al. Alternative O-GlcNAcylation/O-phosphorylation of Ser16 induce different conformational disturbances to the N terminus of murine estrogen receptor β. Chem. Biol. 13, 937–944 (2006).

    Article  CAS  PubMed  Google Scholar 

  54. Ozcan, S., Andrali, S. S. & Cantrell, J. E. Modulation of transcription factor function by O-GlcNAc modification. Biochim. Biophys. Acta 1799, 353–364, (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646–674 (2011).

    Article  CAS  PubMed  Google Scholar 

  56. Wang, Z., Gucek, M. & Hart, G. W. Cross-talk between GlcNAcylation and phosphorylation: site-specific phosphorylation dynamics in response to globally elevated O-GlcNAc. Proc. Natl Acad. Sci. USA 105, 13793–13798 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Hollstein, M. et al. Database of p53 gene somatic mutations in human tumors and cell lines. Nucleic Acids Res. 22, 3551–3555 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Brady, C. A. & Attardi, L. D. p53 at a glance. J. Cell Sci. 123, 2527–2532 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Jones, S. N., Roe, A. E., Donehower, L. A. & Bradley, A. Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53. Nature 378, 206–208 (1995).

    Article  CAS  PubMed  Google Scholar 

  60. Jones, N. C. et al. Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function. Nature Med. 14, 125–133 (2008).

    Article  CAS  PubMed  Google Scholar 

  61. Dai, C. & Gu, W. p53 post-translational modification: deregulated in tumorigenesis. Trends Mol. Med. 16, 528–536 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Chao, C., Herr, D., Chun, J. & Xu, Y. Ser18 and 23 phosphorylation is required for p53-dependent apoptosis and tumor suppression. EMBO J. 25, 2615–2622 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Bech-Otschir, D. et al. COP9 signalosome-specific phosphorylation targets p53 to degradation by the ubiquitin system. EMBO J. 20, 1630–1639 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Yang, W. H. et al. Modification of p53 with O-linked N-acetylglucosamine regulates p53 activity and stability. Nature Cell Biol. 8, 1074–1083 (2006).

    Article  CAS  PubMed  Google Scholar 

  65. Gregory, M. A., Qi, Y. & Hann, S. R. Phosphorylation by glycogen synthase kinase-3 controls c-myc proteolysis and subnuclear localization. J. Biol. Chem. 278, 51606–51612 (2003).

    Article  CAS  PubMed  Google Scholar 

  66. Chou, T. Y., Dang, C. V. & Hart, G. W. Glycosylation of the c-Myc transactivation domain. Proc. Natl Acad. Sci. USA 92, 4417–4421 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Chou, T. Y., Hart, G. W. & 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).

    Article  CAS  PubMed  Google Scholar 

  68. Vervoorts, J., Luscher-Firzlaff, J. & Luscher, B. The ins and outs of MYC regulation by posttranslational mechanisms. J. Biol. Chem. 281, 34725–34729 (2006).

    Article  CAS  PubMed  Google Scholar 

  69. Kamemura, K., Hayes, B. K., Comer, F. I. & Hart, G. W. Dynamic interplay between O-glycosylation and O-phosphorylation of nucleocytoplasmic proteins: alternative glycosylation/phosphorylation of THR-58, a known mutational hot spot of c-Myc in lymphomas, is regulated by mitogens. J. Biol. Chem. 277, 19229–19235 (2002).

    Article  CAS  PubMed  Google Scholar 

  70. Egle, A., Harris, A. W., Bouillet, P. & Cory, S. Bim is a suppressor of Myc-induced mouse B cell leukemia. Proc. Natl Acad. Sci. USA 101, 6164–6169 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Hemann, M. T. et al. Evasion of the p53 tumour surveillance network by tumour-derived MYC mutants. Nature 436, 807–811 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Dias, W. B., Cheung, W. D., Wang, Z. & Hart, G. W. Regulation of calcium/calmodulin-dependent kinase IV by O-GlcNAc modification. J. Biol. Chem. 284, 21327–21337 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Zeidan, Q. & Hart, G. W. The intersections between O-GlcNAcylation and phosphorylation: implications for multiple signaling pathways. J. Cell Sci. 123, 13–22 (2010).

    Article  CAS  PubMed  Google Scholar 

  74. Lazarus, M. B., Nam, Y., Jiang, J., Sliz, P. & Walker, S. Structure of human O-GlcNAc transferase and its complex with a peptide substrate. Nature 469, 564–567 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Kreppel, L. K., Blomberg, M. A. & Hart, G. W. Dynamic glycosylation of nuclear and cytosolic proteins. Cloning and characterization of a unique O-GlcNAc transferase with multiple tetratricopeptide repeats. J. Biol. Chem. 272, 9308–9315 (1997).

    Article  CAS  PubMed  Google Scholar 

  76. Yang, X. et al. Phosphoinositide signalling links O-GlcNAc transferase to insulin resistance. Nature 451, 964–969 (2008).

    Article  CAS  PubMed  Google Scholar 

  77. Kreppel, L. K. & Hart, G. W. Regulation of a cytosolic and nuclear O-GlcNAc transferase. Role of the tetratricopeptide repeats. J. Biol. Chem. 274, 32015–32022 (1999).

    Article  CAS  PubMed  Google Scholar 

  78. Cetinbas, N., Macauley, M. S., Stubbs, K. A., Drapala, R. & Vocadlo, D. J. Identification of Asp174 and Asp175 as the key catalytic residues of human O-GlcNAcase by functional analysis of site-directed mutants. Biochemistry 45, 3835–3844 (2006).

    Article  CAS  PubMed  Google Scholar 

  79. Rao, F. V. et al. Structural insights into the mechanism and inhibition of eukaryotic O-GlcNAc hydrolysis. EMBO J. 25, 1569–1578 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. He, Y., Macauley, M. S., Stubbs, K. A., Vocadlo, D. J. & Davies, G. J. Visualizing the reaction coordinate of an O-GlcNAc hydrolase. J. Am. Chem. Soc. 132, 1807–1809 (2010).

    Article  CAS  PubMed  Google Scholar 

  81. Toleman, C., Paterson, A. J., Whisenhunt, T. R. & Kudlow, J. E. Characterization of the histone acetyltransferase (HAT) domain of a bifunctional protein with activable O-GlcNAcase and HAT activities. J. Biol. Chem. 279, 53665–53673 (2004).

    Article  CAS  Google Scholar 

  82. Butkinaree, C. et al. Characterization of β-N-acetylglucosaminidase cleavage by caspase-3 during apoptosis. J. Biol. Chem. 283, 23557–23566 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Yuzwa, S. A. et al. A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo. Nature Chem. Biol. 4, 483–490 (2008).

    Article  CAS  Google Scholar 

  84. Dorfmueller, H. C. & van Aalten, D. M. Screening-based discovery of drug-like O-GlcNAcase inhibitor scaffolds. FEBS Lett. 584, 694–700 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Dephoure, N. et al. A quantitative atlas of mitotic phosphorylation. Proc. Natl Acad. Sci. USA 105, 10762–10767 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Lengauer, C., Kinzler, K. W. & Vogelstein, B. Genetic instability in colorectal cancers. Nature 386, 623–627 (1997).

    Article  CAS  PubMed  Google Scholar 

  87. Adams, R. R., Maiato, H., Earnshaw, W. C. & Carmena, M. Essential roles of Drosophila inner centromere protein (INCENP) and aurora B in histone H3 phosphorylation, metaphase chromosome alignment, kinetochore disjunction, and chromosome segregation. J. Cell Biol. 153, 865–880 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Wells, L., Kreppel, L. K., Comer, F. I., Wadzinski, B. E. & Hart, G. W. O-GlcNAc transferase is in a functional complex with protein phosphatase 1 catalytic subunits. J. Biol. Chem. 279, 38466–38470 (2004).

    Article  CAS  PubMed  Google Scholar 

  89. Sugiyama, K. et al. Aurora-B associated protein phosphatases as negative regulators of kinase activation. Oncogene 21, 3103–3111 (2002).

    Article  CAS  PubMed  Google Scholar 

  90. Iyer, S. P., Akimoto, Y. & Hart, G. W. Identification and cloning of a novel family of coiled-coil domain proteins that interact with O-GlcNAc transferase. J. Biol. Chem. 278, 5399–5409 (2003).

    Article  CAS  PubMed  Google Scholar 

  91. Iyer, S. P. & Hart, G. W. Roles of the tetratricopeptide repeat domain in O-GlcNAc transferase targeting and protein substrate specificity. J. Biol. Chem. 278, 24608–24616 (2003).

    Article  CAS  PubMed  Google Scholar 

  92. Beck, M. et al. Identification, molecular cloning, and characterization of a novel GABAA receptor-associated protein, GRIF-1. J. Biol. Chem. 277, 30079–30090 (2002).

    Article  CAS  PubMed  Google Scholar 

  93. Wells, L. et al. Dynamic O-glycosylation of nuclear and cytosolic proteins: further characterization of the nucleocytoplasmic β-N-acetylglucosaminidase, O-GlcNAcase. J. Biol. Chem. 277, 1755–1761 (2002).

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank K. Sakabe and Q. Zeidan for critical reading of the manuscript. Research is supported by the US National Institutes of Health (R01 DK61671; R01 CA42486; R24 DK084949), the Patrick C. Walsh Prostate Cancer Research Fund, and by N01-HV-00240 to G.W.H. and P20RR024214 to C.S..

Author information

Authors and Affiliations

  1. Chad Slawson is at The Department of Biochemistry and Molecular Biology, Kansas University School of Medicine, 3,901 Rainbow Boulevard, Kansas City, Kansas 66160, USA.,

    Chad Slawson

  2. Gerald W. Hart is at The Department of Biological Chemistry, The Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, Maryland 21205, USA.,

    Gerald W. Hart

Authors
  1. Chad Slawson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gerald W. Hart
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gerald W. Hart.

Ethics declarations

Competing interests

G.W.H. receives a share of royalty received by the university on sales of the CTD 110.6 anti-O-GlcNAc antibody. Terms of this arrangement are managed by JHUSOM. This antibody is also provided free to any academic who requests it.

Related links

Related links

FURTHER INFORMATION

Chad Slawson's homepage

Gerald W. Hart's homepage

dbOGAP: Database of O-GlcNAcylated Proteins and Sites

Rights and permissions

Reprints and permissions

About this article

Cite this article

Slawson, C., Hart, G. O-GlcNAc signalling: implications for cancer cell biology. Nat Rev Cancer 11, 678–684 (2011). https://doi.org/10.1038/nrc3114

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrc3114

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer