Galactosylation of N-linked oligosaccharides by human  -1,4-galactosyltransferases I, II, III, IV, V, and VI expressed in Sf-9 cells

Guo, Shanchun; Satô, Takeshi; Shirane, Katsunori; Furukawa, Kiyoshi

doi:10.1093/glycob/11.10.813

Cited by 78 publications

(57 citation statements)

References 39 publications

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“…One of the most prominent transformation-associated changes in the sugar chains of glycoproteins is an increase in the large N-glycans of cell surface glycoprotein (2). ␤1,4-galactosyltransferase (GalT) 2 family are the enzymes responsible for the biosynthesis of N-acetyllactosamine on N-glycans by transferring UDP-galactose to the terminal N-acetylglusamine (N-GlcNAc) residues, and this family consist of seven members, from GalT I to GalT VII (3,4).…”

Section: From the Key Laboratory Of Medical Molecular Virology Ministmentioning

confidence: 99%

β1,4-Galactosyltransferase V Functions as a Positive Growth Regulator in Glioma

Jiang

Chen

Shen

et al. 2006

Journal of Biological Chemistry

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␤1,4-galactosyltransferase V (GalT V; EC 2.4.1.38) can effectively galactosylate the GlcNAc␤13 6Man arm of the highly branched N-glycans that are characteristic of glioma. Previously, we have reported that the expression of GalT V is increased in the process of glioma. However, currently little is known about the role of GalT V in this process. In this study, the ectopic expression of GalT V could promote the invasion and survival of glioma cells and transformed astrocytes. Furthermore, decreasing the expression of GalT V in glioma cells promoted apoptosis, inhibited the invasion and migration and the ability of tumor formation in vivo, and reduced the activation of AKT. In addition, the activity of GalT V promoter could be induced by epidermal growth factor, dominant active Ras, ERK1, JNK1, and constitutively active AKT. Taken together, our results suggest that GalT V functioned as a novel glioma growth activator and might represent a novel target in glioma therapy.The carbohydrate moieties of cell surface glycoconjugates play an important role in cell adhesion and metastasis (1). One of the most prominent transformation-associated changes in the sugar chains of glycoproteins is an increase in the large N-glycans of cell surface glycoprotein (2). ␤1,4-galactosyltransferase (GalT) 2 family are the enzymes responsible for the biosynthesis of N-acetyllactosamine on N-glycans by transferring UDP-galactose to the terminal N-acetylglusamine (N-GlcNAc) residues, and this family consist of seven members, from GalT I to GalT VII (3,4).GalT V, a member of ␤1,4-galactosyltransferase (GalT) family, could effectively galactosylate the GlcNAc␤136 branch (5), which is a marker of glioma (6). The expression change of GalT V has been investigated using NIH3T3 and the highly malignant transformed cell line MTAg. Northern blot analysis has revealed that the transcript of GalT V gene increases by 2-3-fold in the transformed cells (7). Similar results have been obtained in several human cancer cell lines (8). Consistently, our previous study has shown that the expression of GalT V is increased in the process of glioma development, with the highest level in grade IV glioma (9). Despite this knowledge, currently little is known about the role of GalT V in the process of glioma formation.The experiments reported here were undertaken to further study the role of GalT V in glioma malignancy, including cell migration, invasion, growth, and survival. Our results indicate that GalT V functioned as a novel glioma growth activator and could represent a novel target in glioma therapy. EXPERIMENTAL PROCEDURESMaterials-Restriction enzymes, bovine calf serum, fetal bovine serum (FBS), DMEM, RPMI 1640 medium, and TRIzol reagent were from Invitrogen. G418, phenylmethylsulfonyl fluoride, aprotinin, pepstatin, epidermal growth factor (EGF), etoposide (VP16), and toluidine blue O were from Sigma. [␥-32 P]dATP and the ECL assay kit were from Amersham Biosciences. Sialidase was from Roche Applied Science. The following antibodies were purchased from Sa...

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Section: From the Key Laboratory Of Medical Molecular Virology Ministmentioning

confidence: 99%

β1,4-Galactosyltransferase V Functions as a Positive Growth Regulator in Glioma

Jiang

Chen

Shen

et al. 2006

Journal of Biological Chemistry

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“…In contrast, no significant changes in the specific activities of other glycosyltransferases involved in the biosynthesis of N-glycans have been observed in transformed cells (15,17). Because the Gal␤134GlcNAc outer chains form the basis for the expression of a variety of carbohydrate antigens, whether or not the gene expression of UDP-Gal:GlcNAc ␤-1,4-galactosyltransferases (␤-1,4-GalT) I-VI, most of which are involved in the biosynthesis of N-glycans (18,19), is changed by malignant transformation was investigated using NIH3T3 and MTAg cells as described above. Northern blot analysis revealed that the ␤-1,4-GalT V transcript increases 2-3-fold and the ␤-1,4-GalT II transcript decreases to one-tenth, whereas those of other ␤-1,4-GalTs remain constant upon malignant transformation (17).…”

Section: Takeshi Sato ‡ and Kiyoshi Furukawamentioning

confidence: 99%

Transcriptional Regulation of the Human β-1,4-Galactosyltransferase V Gene in Cancer Cells

Satô

Furukawa

2004

Journal of Biological Chemistry

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“…4). As human β4GalT1 has been shown to be involved in the β4-galactosylation of highly branched N-glycans, 35,36) the binding of RCA-I and L-PHA, both of which interact with the β4-galactosylated N-glycans, 28,29) decreased significantly in the Sp1-downregulated cells as the results of the reduced expression of the β4GalT1 gene (Figs. 2, 4).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Transcription Factor Sp1 Suppresses Malignant Properties of A549 Human Lung Cancer Cell Line with Decreased β4-Galactosylation of Highly Branched <i>N</i>-Glycans

Muramoto

Tange

Ishii

et al. 2017

Biological & Pharmaceutical Bulletin

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Dramatic changes in the glycan structures of cell surface proteins have been observed upon malignant transformation of cells as induced by the altered expression levels of glycosyltransferases. Such changes are closely associated with the malignant properties of cancer cells. Transcription factor Sp1 regulates the gene expression of various molecules including glycosyltransferases. Herein, we investigated whether or not Sp1-downregulation affects to N-glycosylation of glycoproteins and malignant properties of A549 human lung cancer cell line. We established a stable clone whose Sp1-expression level was reduced to 50% of a control clone by RNA interference. Lectin blotting revealed that the β4-galactosylation of highly branched N-glycans decreases mainly in cell adhesion molecule, E-cadherin. The analysis of underlying mechanism for decreased β4-galactosylation of N-glycans showed that the gene expression level of β4-galactosyltransferase (β4GalT) 1 decreases dramatically by downregulation of Sp1 without changes in those of β4GalT2 and N-acetylglucosaminyltransferase V. Mutations in the Sp1-binding sites of the β4GalT1 gene promoter showed that the promoter activity decreases significantly, indicating that the gene expression is regulated by Sp1. These results indicate that the β4-galactosylation of highly branched N-glycans decreases by downregulation of Sp1 through the reduced expression of the β4GalT1 gene. Furthermore, the Sp1-downregulated cells showed the suppression of the anchorage-independent growth in soft agar and migratory activity when compared to the control cells. The present study demonstrates that downregulation of Sp1 suppresses the malignant properties of A549 cells through the decreased β4-galactosylation of highly branched N-glycans. Key words Sp1; N-glycan; β4-galactosylation; β4-galactosyltransferase 1; lung cancer; malignant propertyIn general, the carbohydrate structures of glycans attached to cell surface proteins change dramatically by malignant transformation.1,2) The most prominent change is the increment of highly branched N-glycans containing the Galβ1 4GlcNAcβ1 6Man group, which is synthesized by N-acetylglucosaminyltransferase (GlcNAcT) V and β4-galactosyltransferase (β4GalT). The increment of highly branched N-glycans is associated with malignant properties of cancer cells.3,4) On the other hand, the GlcNAcT V-deficient mice, in which the amounts of highly branched N-glycans are reduced, showed that the growth and metastasis of mammary tumor induced by polyoma virus middle T oncogene are suppressed.5) Therefore, the biosynthetic pathway of highly branched N-glycans is considered to be important for expressing the malignant properties of cancer cells.The gene expression levels of several glycosyltransferases including GlcNAcT IVa, GlcNAcT V, β4GalT1, β4GalT5, fucosyltransferase (FUT) I, FUT II, and α-2,6-sialyltransferase I have been shown to increase in cancer cells, [6][7][8][9][10][11][12] and the changes in glycosylation induced by the altered expression levels of the glycosyl...

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Galactosylation of N-linked oligosaccharides by human -1,4-galactosyltransferases I, II, III, IV, V, and VI expressed in Sf-9 cells

Cited by 78 publications

References 39 publications

β1,4-Galactosyltransferase V Functions as a Positive Growth Regulator in Glioma

β1,4-Galactosyltransferase V Functions as a Positive Growth Regulator in Glioma

Transcriptional Regulation of the Human β-1,4-Galactosyltransferase V Gene in Cancer Cells

Downregulation of Transcription Factor Sp1 Suppresses Malignant Properties of A549 Human Lung Cancer Cell Line with Decreased β4-Galactosylation of Highly Branched <i>N</i>-Glycans

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