Advertisement

Beta-1,3-Galactosyl-O-Glycosyl-Glycoprotein Beta-1,6-N-Acetylglucosaminyltransferase 3 (GCNT3)

  • Jiunn-Chern (Gene) Yeh
  • Minoru Fukuda
Reference work entry

Abstract

GCNT3 (C2GnT2/M) is a unique glycosyltransferase in having multiple enzymatic activities (Yeh et al. 1999; Schwientek et al. 1999). It was shown to have core2 and core4 branching as well as I branching, mainly dIGnT, enzymatic activities. GCNT3 is the only glycosyltransferase identified up-to-date to possess core4GnT activity. This is in line with the observations that the presence of core4GnT activity is always associated with core2GnT activity (Brockhausen et al. 1986; Ropp et al. 1991; Yang et al. 1994; Vavasseur et al. 1995). GCNT3 is highly expressed in mucin-producing tissues (Yeh et al. 1999; Schwientek et al. 1999), indicating a pivotal role in mucosal functions.

Keywords

Dextran Sodium Sulfate Mucosal Function Multiple Enzymatic Activity Sole Enzyme Triple Knockout Mouse 
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.

References

  1. An G, Wei B, Xia B, McDaniel JM, Ju T, Cummings RD, Braun J, Xia L (2007) Increased susceptibility to colitis and colorectal tumors in mice lacking core 3-derived O-glycans. J Exp Med 204(6):1417–1429PubMedCentralPubMedCrossRefGoogle Scholar
  2. Aoki D, Lee N, Yamaguchi N, Dubois C, Fukuda MN (1992) Golgi retention of a trans-Golgi membrane protein, galactosyltransferase, requires cysteine and histidine residues within the membrane-anchoring domain. Proc Natl Acad Sci 89(10):4319–4323PubMedCrossRefGoogle Scholar
  3. Beum PV, Bastola DR, Cheng PW (2003) Mucin biosynthesis: epidermal growth factor downregulates core 2 enzymes in a human airway adenocarcinoma cell line. Am J Respir Cell Mol Biol 29(1):48–56PubMedCrossRefGoogle Scholar
  4. Beum PV, Basma H, Bastola DR, Cheng PW (2005) Mucin biosynthesis: upregulation of core 2 beta 1,6 N-acetylglucosaminyltransferase by retinoic acid and Th2 cytokines in a human airway epithelial cell line. Am J Physiol Lung Cell Mol Physiol 288(1):L116–L124PubMedCrossRefGoogle Scholar
  5. 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 USA 89:9326–9330PubMedCrossRefGoogle Scholar
  6. Bierhuizen MF, Mattei MG, Fukuda M (1993) Expression of the developmental I antigen by a cloned human cDNA encoding a member of a beta-1,6-N-acetylglucosaminyltransferase gene family. Genes Dev 7(3):468–478PubMedCrossRefGoogle Scholar
  7. Brockhausen I, Matta KL, Orr J, Schachter H, Koenderman AH, van den Eijnden DH (1986) Mucin synthesis. Conversion of R1-beta 1-3Gal-R2 to R1-beta 1-3(GlcNAc beta 1-6)Gal-R2 and of R1-beta 1-3GalNAc-R2 to R1-beta 1-3(GlcNAc beta 1-6)GalNAc-R2 by a beta 6-N-acetylglucosaminyltransferase in pig gastric mucosa. Eur J Biochem 157(3):463–474PubMedCrossRefGoogle Scholar
  8. Chen GY, Muramatsu H, Kondo M, Kurosawa N, Miyake Y, Takeda N, Muramatsu T (2005) Abnormalities caused by carbohydrate alterations in Ibeta6-N-acetylglucosaminyltransferase-deficient mice. Mol Cell Biol 25(17):7828–7838PubMedCentralPubMedCrossRefGoogle Scholar
  9. Cheng PW, Radhakrishnan P (2011) Mucin O-Glycan branching enzymes: structure, function, and gene regulation. Adv Exp Med Biol 705:465–492PubMedCrossRefGoogle Scholar
  10. Choi KH, Osorio FA, Cheng PW (2004) Mucin biosynthesis: bovine C2GnT-M gene, tissue-specific expression, and herpes virus-4-homologue. Am J Respir Cell Mol Biol 30(5):710–719PubMedCrossRefGoogle Scholar
  11. 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(6):881–890PubMedCrossRefGoogle Scholar
  12. Gu J, Nishikawa A, Fujii S, Gasa S, Taniguchi N (1992) Biosynthesis of blood group I and i antigens in rat tissues. Identification of a novel beta 1-6-N-acetylglucosaminyltransferase. J Biol Chem 267:2994–2999PubMedGoogle Scholar
  13. Hashimoto M, Tan S, Mori N, Cheng H, Cheng PW (2007) Mucin biosynthesis: molecular cloning and expression of mouse mucus-type core 2 beta1,6 N-acetylglucosaminyltransferase. Glycobiology 17(9):994–1006PubMedCrossRefGoogle Scholar
  14. Huang MC, Chen HY, Huang HC, Huang J, Liang JT, Shen TL, Lin NY, Ho CC, Cho IM, Hsu SM (2006) C2GnT-M is downregulated in colorectal cancer and its re-expression causes growth inhibition of colon cancer cells. Oncogene 25(23):3267–3276PubMedCrossRefGoogle Scholar
  15. Ismail MN, Stone EL, Panico M, Lee SH, Luu Y, Ramirez K, Ho SB, Fukuda M, Marth JD, Haslam SM, Dell A (2011) High-sensitivity O-glycomic analysis of mice deficient in core 2 {beta}1,6-N-acetylglucosaminyltransferases. Glycobiology 21(1):82–98PubMedCrossRefGoogle Scholar
  16. Ishibashi Y, Inouye Y, Okano T, Taniguchi A (2005) Regulation of sialyl-Lewis x epitope expression by TNF-alpha and EGF in an airway carcinoma cell line. Glycoconj J 22:53–62. doi:10.1007/s10719-005-0292-7PubMedCrossRefGoogle Scholar
  17. Korekane H, Taguchi T, Sakamoto Y, Honke K, Dohmae N, Salminen H, Toivonen S, Helin J, Takio K, Renkonen O, Taniguchi N (2003) Purification and cDNA cloning of UDP-GlcNAc: GlcNAcbeta1-3Galbeta1-4Glc(NAc)-R [GlcNAc to Gal]beta1,6N-acetylglucosaminyltransferase from rat small intestine: a major carrier of dIGnT activity in rat small intestine. Glycobiology 13:387–400PubMedCrossRefGoogle Scholar
  18. Lee SH, Yu SY, Nakayama J, Khoo KH, Stone EL, Fukuda MN, Marth JD, Fukuda M (2010) Core2 O-glycan structure is essential for the cell surface expression of sucrase isomaltase and dipeptidyl peptidase-IV during intestinal cell differentiation. J Biol Chem 285(48):37683–37692PubMedCrossRefGoogle Scholar
  19. Markine-Goriaynoff N, Georgin JP, Goltz M, Zimmermann W, Broll H, Wamwayi HM, Pastoret PP, Sharp PM, Vanderplasschen A (2003) The core 2 beta-1,6-N-acetylglucosaminyltransferase-mucin encoded by bovine herpesvirus 4 was acquired from an ancestor of the African buffalo. J Virol 77(3):1784–1792PubMedCentralPubMedCrossRefGoogle Scholar
  20. Markine-Goriaynoff N, Gillet L, Karlsen OA, Haarr L, Minner F, Pastoret PP, Fukuda M, Vanderplasschen A (2004) The core 2 beta-1,6-N-acetylglucosaminyltransferase-M encoded by bovine herpesvirus 4 is not essential for virus replication despite contributing to post-translational modifications of structural proteins. J Gen Virol 85:355–367PubMedCrossRefGoogle Scholar
  21. McBride DS, Brockhausen I, Kan FW (2005) Detection of glycosyltransferases in the golden hamster (Mesocricetus auratus) oviduct and evidence for the regulation of O-glycan biosynthesis during the estrous cycle. Biochim Biophys Acta 1721(1–3):107–115PubMedCrossRefGoogle Scholar
  22. Mullaly SC, Oudhoff MJ, Min PH, Burrows K, Antignano F, Rattray DG, Chenery A, McNagny KM, Ziltener HJ, Zaph C (2013) Requirement for core 2 o-glycans for optimal resistance to helminth infection. PLoS One 8(3):e60124PubMedCentralPubMedCrossRefGoogle Scholar
  23. Pak JE, Arnoux P, Zhou S, Sivarajah P, Satkunarajah M, Xing X, Rini JM (2006) X-ray crystal structure of leukocyte type core 2 beta1,6-N-acetylglucosaminyltransferase. Evidence for a convergence of metal ion-independent glycosyltransferase mechanism. J Biol Chem 281:26693–26701PubMedCrossRefGoogle Scholar
  24. Pak JE, Arnoux P, Zhou S, Sivarajah P, Satkunarajah M, Xing X, Rini JM (2011) Structural and mechanistic characterization of leukocyte-type core 2 β1,6-N-acetylglucosaminyltransferase: a metal-ion-independent GT-A glycosyltransferase. J Mol Biol 414:798–811PubMedCrossRefGoogle Scholar
  25. Radhakrishnan P, Beum PV, Tan S, Cheng PW (2007) Butyrate induces sLex synthesis by stimulation of selective glycosyltransferase genes. Biochem Biophys Res Commun 359(3):457–462PubMedCentralPubMedCrossRefGoogle Scholar
  26. Ropp PA, Little MR, Cheng PW (1991) Mucin biosynthesis: purification and characterization of a mucin β6 N-acetylglucosaminyltransferase. J Biol Chem 266(35):23863–23871PubMedGoogle Scholar
  27. Schachter H, Brockhausen I (1992) Glycoconjugates: composition, structure, and function. In: Allen HJ, Kisailus EC (eds), 1st edn. Marcel New York, pp 263–332Google Scholar
  28. Schwientek T, Nomoto M, Levery SB, Merkx G, van Kessel AG, Bennett EP, Hollingsworth MA, Clausen H (1999) Control of O-glycan branch formation: molecular cloning of human cDNA encoding a novel beta-1,6-N-acetylglucosaminyltransferase forming core 2 and core 4. J Biol Chem 274:4504–4512PubMedCrossRefGoogle Scholar
  29. 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
  30. Shafi R, Iyer SP, Ellies LG, O'Donnell N, Marek KW, Chui D, Hart GW, Marth JD (2000) The O-GlcNAc transferase gene resides on the X chromosome and is essential for embryonic stem cell viability and mouse ontogeny. Proc Natl Acad Sci USA 97(11):5735–5739PubMedCrossRefGoogle Scholar
  31. Singh J, Khan GA, Kinarsky L, Cheng H, Wilken J, Choi KH, Bedows E, Sherman S, Cheng PW (2004) Identification of disulfide bonds among the nine core 2 N-acetylglucosaminyltransferase-M cysteines conserved in the mucin beta6-N-acetylglucosaminyltransferase family. J Biol Chem 279:38969–38977PubMedCrossRefGoogle Scholar
  32. 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
  33. Tan Sand Cheng PW (2007) Mucin biosynthesis: identification of the cis-regulatory elements of human C2GnT-M gene. Am J Respir Cell Mol Biol 36(6):737–745CrossRefGoogle Scholar
  34. Toki D, Sarkar M, Yip B, Reck F, Joziasse D, Fukuda M, Schachter H, Brockhausen I (1997) Expression of stable human O-glycan core 2 beta-1,6-N-acetylglucosaminyltransferase in Sf9 insect cells. Biochem J 325:63–69PubMedGoogle Scholar
  35. Vanderplasschen A, Markine-Goriaynoff N, Lomonte P, Suzuki M, Hiraoka N, Yeh JC, Bureau F, Willems L, Thiry E, Fukuda M, Pastoret PP (2000) A multipotential beta -1,6-N-acetylglucosaminyl-transferase is encoded by bovine herpesvirus type 4. Proc Natl Acad Sci USA 97(11):5756–5761PubMedCentralPubMedCrossRefGoogle Scholar
  36. Vavasseur F, Yang JM, Dole K, Paulsen H, Brockhausen I (1995) Synthesis of O-glycan core 3: characterization of UDP-GlcNAc: GalNAc-R beta 3-N-acetyl-glucosaminyltransferase activity from colonic mucosal tissues and lack of the activity in human cancer cell lines. Glycobiology 5(3):351–357PubMedCrossRefGoogle Scholar
  37. Yanagihara K, Seki M, Cheng PW (2001) Lipopolysaccharide induces mucus cell metaplasia in mouse lung. Am J Respir Cell Mol Biol 24(1):66–73PubMedCrossRefGoogle Scholar
  38. Yang JM, Byrd JC, Siddiki BB, Chung YS, Okuno M, Sowa M, Kim YS, Matta KL, Brockhausen I (1994) Alterations of O-glycan biosynthesis in human colon cancer tissues. Glycobiology 4(6):873–884PubMedCrossRefGoogle Scholar
  39. 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(5):3215–3221PubMedCrossRefGoogle Scholar
  40. 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 core 1 extension β1,3-N-acetylglucosaminyltransferase. Cell 105:957–969PubMedCrossRefGoogle Scholar
  41. Yen TY, Macher BA, Bryson S, Chang X, Tvaroska I, Tse R, Takeshita S, Lew AM, Datti A (2003) Highly conserved cysteines of mouse core 2 beta1,6-N-acetylglucosaminyltransferase I form a network of disulfide bonds and include a thiol that affects enzyme activity. J Biol Chem 278(46):45864–45881PubMedCrossRefGoogle Scholar
  42. Yu LC, Twu YC, Chou ML, Reid ME, Gray AR, Moulds JM, Chang CY, Lin M (2003) The molecular genetics of the human I locus and molecular background explain the partial association of the adult i phenotype with congenital cataracts. Blood 101(6):2081–2088PubMedCrossRefGoogle Scholar
  43. Zerfaoui M, Fukuda M, Langlet C, Mathieu S, Suzuki M, Lombardo D, El-Battari A (2002) The cytosolic and transmembrane domains of the beta 1,6 N-acetylglucosaminyltransferase (C2GnT) function as a cis to medial/Golgi-targeting determinant. Glycobiology 12(1):15–24PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  1. 1.Sanford-Burnham Medical Research InstituteLa JollaUSA
  2. 2.Tumor Microenvironment ProgramSanford-Burnham Medical Research InstituteLa JollaUSA

Personalised recommendations