Beta-1,3-Galactosyl-O-Glycosyl-Glycoprotein Beta-1,6-N-Acetylglucosaminyltransferase 1 (GCNT1) (C2GnT-L) and Beta-1,3-Galactosyl-O-Glycosyl-Glycoprotein Beta-1,6-N-Acetylglucosaminyltransferase 3 (GCNT4) (C2GnT-T)

Reference work entry


The appearance of a branch Galβ1-3(GlcNAcβ1-6)GalNAc in O-glycans has been demonstrated in many important biological processes such as T cell activation, T cell development, leukemia, immunodeficiencies (Tsuboi and Fukuda 2001), and cancer metastasis (Tsuboi et al. 2012). This branch is formed by a glycosyltransferase, core2 β1-6GlcNAc transferase (designated C2GnT) that catalyzes the transfer of GlcNAc to Galβ1-3GalNAc in O-glycans, resulting in the conversion of Galβ1-3GalNAc, core1 to Galβ1-3(GlcNAcβ1-6)GalNAc, core2 (Fig. 34.1).


High Endothelial Venule Core2 Oligosaccharide Selectin Ligand Core2 Branch Human Promyelocytic Leukemia Cell Line 
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  1. Baum LG, Pang M, Perillo NL, Wu T, Delegeane A, Uittenbogaart CH, Fukuda M, Seilhamer JJ (1995) Human thymic epithelial cells express an endogenous lectin, galectin-1, which binds to core 2 O-glycans on thymocytes and T lymphoblastoid cells. J Exp Med 181:877–887PubMedCrossRefGoogle Scholar
  2. Bierhuizen MF, Fukuda M (1992) Expression cloning of a cDNA encoding UDP-GlcNAc: Gal beta 1-3-GalNAc-R (GlcNAc to GalNAc) beta 1-6GlcNAc transferase by gene transfer into CHO cells expressing polyoma large tumor antigen. Proc Natl Acad Sci U S A 89:9326–9330PubMedCentralPubMedCrossRefGoogle Scholar
  3. Bistrup A, Bhakta S, Lee JK, Belov YY, Gunn MD, Zuo FR, Huang CC, Kannagi R, Rosen SD, Hemmerich S (1999) Sulfotransferases of two specificities function in the reconstitution of high endothelial cell ligands for L-selectin. J Cell Biol 145:899–910PubMedCrossRefGoogle Scholar
  4. Brockhausen I, Kuhns W, Schachter H, Matta KL, Sutherland DR, Baker MA (1991) Biosynthesis of O-glycans in leukocytes from normal donors and from patients with leukemia: increase in O-glycan core 2 UDP-GlcNAc: Gal beta 3 GalNAc alpha-R (GlcNAc to GalNAc) beta(1-6)-N-acetylglucosaminyltransferase in leukemic cells. Cancer Res 51:1257–1263PubMedGoogle Scholar
  5. Ellies LG, Tsuboi S, Petryniak B, Lowe JB, Fukuda M, Marth JD (1998) Core 2 oligosaccharide biosynthesis distinguishes between selectin ligands essential for leukocyte homing and inflammation. Immunity 9:881–890PubMedCrossRefGoogle Scholar
  6. Gauguet JM, Rosen SD, Marth JD, von Andrian UH (2004) Core 2 branching beta1,6-N-acetylglucosaminyltransferase and high endothelial cell N-acetylglucosamine-6-sulfotransferase exert differential control over B- and T-lymphocyte homing to peripheral lymph nodes. Blood 104:4104–4112PubMedCrossRefGoogle Scholar
  7. Hagisawa S, Ohyama C, Takahashi T, Endoh M, Moriya T, Nakayama J, Arai Y, Fukuda M (2005) Expression of core 2 beta1,6-N-acetylglucosaminyltransferase facilitates prostate cancer progression. Glycobiology 15:1016–1024PubMedCrossRefGoogle Scholar
  8. Hatakeyama S, Kyan A, Yamamoto H, Okamoto A, Sugiyama N, Suzuki Y, Yoneyama T, Hashimoto Y, Koie T, Yamada S et al (2010) Core 2 N-acetylglucosaminyltransferase-1 expression induces aggressive potential of testicular germ cell tumor. Int J Cancer 127:1052–1059PubMedCentralPubMedCrossRefGoogle Scholar
  9. Hemmerich S, Leffler H, Rosen SD (1995) Structure of the O-glycans in GlyCAM-1, an endothelial-derived ligand for L-selectin. J Biol Chem 270:12035–12047PubMedCrossRefGoogle Scholar
  10. Higgins EA, Siminovitch KA, Zhuang DL, Brockhausen I, Dennis JW (1991) Aberrant O-linked oligosaccharide biosynthesis in lymphocytes and platelets from patients with the Wiskott-Aldrich syndrome. J Biol Chem 266:6280–6290PubMedGoogle Scholar
  11. Hiraoka N, Kawashima H, Petryniak B, Nakayama J, Mitoma J, Marth JD, Lowe JB, Fukuda M (2004) Core 2 branching beta1,6-N-acetylglucosaminyltransferase and high endothelial venule-restricted sulfotransferase collaboratively control lymphocyte homing. J Biol Chem 279:3058–3067PubMedCrossRefGoogle Scholar
  12. Hiraoka N, Petryniak B, Nakayama J, Tsuboi S, Suzuki M, Yeh JC, Izawa D, Tanaka T, Miyasaka M, Lowe JB et al (1999) A novel, high endothelial venule-specific sulfotransferase expresses 6-sulfo sialyl Lewis(x), an L-selectin ligand displayed by CD34. Immunity 11:79–89PubMedCrossRefGoogle Scholar
  13. Huang MM, Tsuboi S, Wong A, Yu XJ, Oh-Eda M, Derry JM, Francke U, Fukuda M, Weinberg KI, Kohn DB (2000) Expression of human Wiskott-Aldrich syndrome protein in patients’ cells leads to partial correction of a phenotypic abnormality of cell surface glycoproteins. Gene Ther 7:314–320PubMedCrossRefGoogle Scholar
  14. Ismail MN, Stone EL, Panico M, Lee SH, Luu Y, Ramirez K, Ho SB, Fukuda M, Marth JD, Haslam SM et al (2011) High-sensitivity O-glycomic analysis of mice deficient in core 2 {beta}1,6-N-acetylglucosaminyltransferases. Glycobiology 21:82–98PubMedCrossRefGoogle Scholar
  15. Kawashima H, Petryniak B, Hiraoka N, Mitoma J, Huckaby V, Nakayama J, Uchimura K, Kadomatsu K, Muramatsu T, Lowe JB, Fukuda M (2005) N-acetylglucosamine-6-O-sulfotransferases 1 and 2 cooperatively control lymphocyte homing through L-selectin ligand biosynthesis in high endothelial venules. Nat Immunol 6:1096–1104PubMedCrossRefGoogle Scholar
  16. Li F, Wilkins PP, Crawley S, Weinstein J, Cummings RD, McEver RP (1996) Post-translational modifications of recombinant P-selectin glycoprotein ligand-1 required for binding to P- and E-selectin. J Biol Chem 271:3255–3264PubMedCrossRefGoogle Scholar
  17. Machida E, Nakayama J, Amano J, Fukuda M (2001) Clinicopathological significance of core 2 beta1,6-N-acetylglucosaminyltransferase messenger RNA expressed in the pulmonary adenocarcinoma determined by in situ hybridization. Cancer Res 61:2226–2231PubMedGoogle Scholar
  18. Maemura K, Fukuda M (1992) Poly-N-acetyllactosaminyl O-glycans attached to leukosialin. The presence of sialyl Le(x) structures in O-glycans. J Biol Chem 267:24379–24386PubMedGoogle Scholar
  19. Okamoto T, Yoneyama MS, Hatakeyama S, Mori K, Yamamoto H, Koie T, Saitoh H, Yamaya K, Funyu T, Fukuda M et al (2013) Core2 O-glycan-expressing prostate cancer cells are resistant to NK cell immunity. Mol Med Rep 7:359–364PubMedGoogle Scholar
  20. Piller F, Le Deist F, Weinberg KI, Parkman R, Fukuda M (1991) Altered O-glycan synthesis in lymphocytes from patients with Wiskott-Aldrich syndrome. J Exp Med 173:1501–1510PubMedCrossRefGoogle Scholar
  21. Piller F, Piller V, Fox RI, Fukuda M (1988) Human T-lymphocyte activation is associated with changes in O-glycan biosynthesis. J Biol Chem 263:15146–15150PubMedGoogle Scholar
  22. Saitoh O, Piller F, Fox RI, Fukuda M (1991) T-lymphocytic leukemia expresses complex, branched O-linked oligosaccharides on a major sialoglycoprotein, leukosialin. Blood 77:1491–1499PubMedGoogle Scholar
  23. Schwientek T, Yeh JC, Levery SB, Keck B, Merkx G, van Kessel AG, Fukuda M, Clausen H (2000) Control of O-glycan branch formation. Molecular cloning and characterization of a novel thymus-associated core 2 beta1, 6-n-acetylglucosaminyltransferase. J Biol Chem 275:11106–11113PubMedCrossRefGoogle Scholar
  24. Shimodaira K, Nakayama J, Nakamura N, Hasebe O, Katsuyama T, Fukuda M (1997) Carcinoma-associated expression of core 2 beta-1,6-N-acetylglucosaminyltransferase gene in human colorectal cancer: role of O-glycans in tumor progression. Cancer Res 57:5201–5206PubMedGoogle Scholar
  25. Stone EL, Ismail MN, Lee SH, Luu Y, Ramirez K, Haslam SM, Ho SB, Dell A, Fukuda M, Marth JD (2009) Glycosyltransferase function in core 2-type protein O glycosylation. Mol Cell Biol 29:3770–3782PubMedCentralPubMedCrossRefGoogle Scholar
  26. Suzuki Y, Sutoh M, Hatakeyama S, Mori K, Yamamoto H, Koie T, Saitoh H, Yamaya K, Funyu T, Habuchi T et al (2012) MUC1 carrying core 2 O-glycans functions as a molecular shield against NK cell attack, promoting bladder tumor metastasis. Int J Oncol 40:1831–1838PubMedCentralPubMedGoogle Scholar
  27. Tsuboi S (2012) Tumor defense systems using O-glycans. Biol Pharm Bull 35:1633–1636PubMedCrossRefGoogle Scholar
  28. Tsuboi S, Fukuda M (1997) Branched O-linked oligosaccharides ectopically expressed in transgenic mice reduce primary T-cell immune responses. EMBO J 16:6364–6373PubMedCrossRefGoogle Scholar
  29. Tsuboi S, Fukuda M (1998) Overexpression of branched O-linked oligosaccharides on T cell surface glycoproteins impairs humoral immune responses in transgenic mice. J Biol Chem 273:30680–30687PubMedCrossRefGoogle Scholar
  30. Tsuboi S, Fukuda M (2001) Roles of O-linked oligosaccharides in immune responses. Bioessays 23:46–53PubMedCrossRefGoogle Scholar
  31. Tsuboi S, Hatakeyama S, Ohyama C, Fukuda M (2012) Two opposing roles of O-glycans in tumor metastasis. Trends Mol Med 18:224–232PubMedCentralPubMedCrossRefGoogle Scholar
  32. Tsuboi S, Sutoh M, Hatakeyama S, Hiraoka N, Habuchi T, Horikawa Y, Hashimoto Y, Yoneyama T, Mori K, Koie T et al (2011) A novel strategy for evasion of NK cell immunity by tumours expressing core2 O-glycans. EMBO J 30:3173–3185PubMedCrossRefGoogle Scholar
  33. Yeh JC, Hiraoka N, Petryniak B, Nakayama J, Ellies LG, Rabuka D, Hindsgaul O, Marth JD, Lowe JB, Fukuda M (2001) Novel sulfated lymphocyte homing receptors and their control by a Core1 extension beta 1,3-N-acetylglucosaminyltransferase. Cell 105:957–969PubMedCrossRefGoogle Scholar
  34. Yeh JC, Ong E, Fukuda M (1999) Molecular cloning and expression of a novel beta-1, 6-N-acetylglucosaminyltransferase that forms core 2, core 4, and I branches. J Biol Chem 274:3215–3221PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  1. 1.Department of Cancer Immunology and Cell BiologyOyokyo Kidney Research InstituteHirosakiJapan
  2. 2.Sanford-Burnham Medical Research InstituteLa JollaUSA

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