Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.4.99.6 (sialyltransferase)
1,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased sialylation, especially involving the Sialyl-Lewisa and Sialyl-Lewisx determinants, has been reported in breast cancer. A multiplex reverse transcription-PCR method was used here to determine the expression of five sialyltransferases (ST3Gal III, ST6Gal I, ST3Gal IV, ST3Gal I, and ST3Gal II) in 49 patients surgically treated for locoregional breast cancer. We assessed the relationship between these expressions and clinical, pathological, and biological features. The most expressed sialyltransferase was ST3Gal 1II, which is involved in Sialyl-Lewisa synthesis. ST3Gal III expression was positively correlated to ST6Gal I and ST3Gal IV expressions, to tumor size, and to the number of involved axillary nodes. Patients with high ST3Gal III expression had a shorter overall survival. High ST6Gal I expression was associated with histoprognostic grade III. ST6Gal I expression was negatively correlated to expression of progesterone receptor. In conclusion, high ST3Gal III and ST6Gal I expressions in human breast tumors are associated with poor prognosis markers.
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PMID:Multiplex reverse transcription polymerase chain reaction assessment of sialyltransferase expression in human breast cancer. 975 11

Hamster cell lines are common hosts for recombinant protein production, e.g. erythropoietin (Epo). Terminal sialylation of native human proteins is characteristically in both alpha-2,3 and alpha-2,6 linkage to galactose at the termini of N-linked oligosaccharides but only in alpha-2,3 linkage in recombinant proteins expressed in hamster cells which do not express alpha-2, 6-sialyltransferase (ST6GalI) (EC 2.4.99.1). This difference could alter the bioactivity of certain recombinant proteins. Chinese hamster ovary (CHO) cells stably transfected with human ST6GalI cDNA linked to the hamster metallothionein II promoter expressed highly inducible authentic ST6GalI activity. Untransfected CHO cells and CHO cells stably expressing ST6GalI cDNA when transfected with a human Epo cDNA expression cassette secreted immunoreactive Epo. Human Epo from singly transfected Pro-5 CHO cells induced significant reticulocytosis (7.00+/-1.58%; mean+/-S.D. % reticulocytes; control conditioned medium 3.04+/-1.29%; P<0.0024), whereas Epo from Pro-5 cells coexpressing ST6GalI elicited a more modest reticulocytosis (4.62+/-1.02%). Thus for recombinant human Epo, engineering CHO cells to express ST6GalI activity does not enhance Epo bioactivity in vivo in mice. The availability of CHO cells that express high levels of ST6GalI activity now enables systematic studies to determine the functional requirement for this form of sialylation in recombinant human proteins.
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PMID:Stable expression of human alpha-2,6-sialyltransferase in Chinese hamster ovary cells: functional consequences for human erythropoietin expression and bioactivity. 983 8

We have investigated the role of sialylation on cell-cell adhesion mediated by E-cadherin. Two MCF-7 human breast cancer cell variants were studied: MCF-7/AZ cells showed a spontaneous cell-cell adhesion in the fast and slow aggregation assay. whereas the adhesion deficient MCF-7/6 cell variant failed to form larger aggregates, suggesting that E-cadherin was not functional under the conditions of both assays. We measured the sialyltransferase activities using Galbeta1-3GalNAcalpha-O-benzyl and Galbeta1-4GlcNAcalpha-O-benzyl as acceptor substrates as well as mRNA levels of four sialyltransferases, ST3Gal I, ST3Gal III, ST3Gal IV, ST6Gal I, using multiplex RT-PCR in MCF-7 cell variants. The alpha2-6 and alpha2-3 sialylation of E-cadherin was investigated by immuno-blot using Sambucus nigra agglutinin and Maackia amurensis agglutinin. Compared to the adhesion-proficient MCF-7/AZ cells, the adhesion-deficient MCF-7/6 cell line apparently lacks ST6Gal I mRNA, has a lower ST3Gal I mRNA, a lower ST3Gal I sialyltransferase activity, and no alpha2-3 linked sialic acid moieties on E-cadherin. The potential anti-cancer drug 1-O-octadecyl-2-O-methylglycero-3-phosphocholine (ET-18-OMe, 48 h, 25 microg/ml) belonging to the class of alkyllysophospholipids restored the E-cadherin function in the adhesion-deficient MCF-7/6 cells as evidenced by an increased aggregation. ET-18-OMe caused loss of ST6Gal I mRNA in MCF-7/AZ cells but no changes of sialyltransferase activities or sialic acid moieties on E-cadherin could be observed. We conclude that Ca2+-dependent, E-cadherin-specific homotypic adhesion of MCF-7/AZ or MCF-7/6 cells treated with ET-18-OMe was not affected by sialylation of E-cadherin.
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PMID:Sialylation of E-cadherin does not change the spontaneous or ET-18-OMe-mediated aggregation of MCF-7 human breast cancer cells. 1043 10

In this study, we report the first isolation and characterization of a bovine sialyltransferase gene. Bovine cDNAs prepared from different tissues contain an open-reading frame encoding a 405 amino acid sequence showing 83%, 75%, and 60% identity with human, murine, and chicken ST6Gal I (beta-galactoside alpha2,6-sialyltransferase) sequences, respectively. When transfected into COS-7 cells, a recombinant enzyme was obtained which catalyzed the in vitro alpha2, 6-sialylation of LacNAc (NeuAcalpha2-6Galbeta1-4GlcNAc) and LacdiNAc (NeuAcalpha2-6GalNAcbeta1-4GlcNAc) acceptor substrates. The K (m) values were 2.8 and 6.9 mM, respectively. Different relative efficiencies (Vmax/Km) for the two precursors (36 for LacNAc and 4.3 for LacdiNAc) were observed. Bovine ST6Gal I gene consists of four 5'-untranslated exons E(-2) to E(1), and five coding exons from E(2) to E(6). This later carries a 3'-untranslated region of 2. 7 kb. Gene sequence spans at least 80 kb of genomic DNA. Two processed pseudogenes have been identified. They are 94.3 and 95.6% similar to the bovine cDNA, respectively. Three families of mRNA isoforms were isolated. They differed by their 5'-untranslated regions and could be generated by three tissue-specific promoters. Family 1 is made up of exons E(-2) and E(1) to E(6), family 2 of exons E(-1) to E(6), and family 3 of exons E(1) to E(6). Tissular distribution of transcript families appears noticeably different than those described in human and rat.
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PMID:Molecular cloning, expression and exon/intron organization of the bovine beta-galactoside alpha2,6-sialyltransferase gene. 1046 Aug 27

A single gene, SIAT1, encodes ST6Gal I, the sialyltransferase that mediates transfer of alpha2,6-linked sialic acids to Galbeta1, 4GlcNAc termini of N-linked glycoproteins. In vivo, multiple SIAT1 mRNA forms, differing only in the 5'-untranslated region, are expressed in a tissue-specific manner. This mRNA heterogeneity has been attributed, at least in part, to transcription from a number of physically distinct promoter regions. In mature B-lymphocytes, SIAT1 transcription initiates at P2, a regulatory region known to function only in B-lineage cells. Bacterial chloramphenicol acetyltransferase (CAT) under the control of the P2 region encompassing 415 bp 5'- and 125 bp 3' of the transcriptional initiation site is efficiently expressed in Louckes, a mature B-lymphoblastoid cell line. In contrast, CAT expression in Reh, a T-null/B-null precursor line, and in HepG2, a hepatoma line, are 14-fold and >25-fold less than in Louckes, respectively. The data is consistent with the presence of cis -acting regulatory elements residing both 5' and 3' of the P2 transcriptional initiation site. At least 370 bp of 5'-flanking sequence, coinciding with the inclusion of AP2 and NF-kappaB sites, is necessary for high level expression in Louckes. Exon sequences 3' of the transcription start site are also important for expression. A segment from(+)32 to(+)125 (position(+)1 is transcription start site) is capable of exerting promoter-like activity in Louckes, but not in Reh or HepG2. CAT expression by P2 is negligible in Reh cells. However, enhanced CAT activity is not accompanied by elevated mRNA levels. This observation is consistent with the relief of translational restraints imposed by the(+)32 to(+)125 region. Together, the data demonstrate that efficient and cell-specific transcription regulation in mature B lymphocytes is contained in a 495 bp P2 segment that is comprised of 370 bp of 5'-flanking region and 125 bp of transcribed region of Exon X.
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PMID:Transcription of the beta-galactoside alpha2,6-sialyltransferase gene (SIAT1) in B-lymphocytes: cell type-specific expression correlates with presence of the divergent 5'-untranslated sequence. 1046 Aug 32

Multiple mRNA isoforms are generated from Siat1, the gene encoding ST6Gal I (beta-galactoside alpha2,6-sialyltransferase, SiaT-1, ST6N, alpha2,6ST). These isoforms, transcriptionally initiated from a number of physically distinct promoter regions, differ only in the 5'-most untranslated region and share an identical ST6Gal I coding region. W16 cells, a spontaneous mutant from MDAY-D2, the highly metastatic murine lymphoid tumor cell line, is considerably less metastatic and exhibits significantly slower tumor growth characteristics [R. Takano, E. Muchmore, and J. W. Dennis (1994) Glycobiology 4, 665-674]. Takano et al. further reported that ST6Gal I mRNA in W16 is elevated 40-fold compared to the parental cells. Here, by means of 5'-RACE analysis, we demonstrate a heretofore undocumented ST6Gal I mRNA form expressed in W16 cells. This ST6Gal I mRNA contains a novel 5'-most untranslated region with 96% sequence similarity to the retroviral-like transposable element, intracisternal particle A (IAP). This observation suggests the notion that elevated ST6Gal I expression in W16 cells is the result of DNA rearrangement in the Siat1 locus. Atypical transcriptional activation of Siat1 is the result of this IAP transposition.
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PMID:Overexpression of the alpha2,6-sialyltransferase, ST6Gal I, in a low metastatic variant of a murine lymphoblastoid cell line is associated with appearance of a unique ST6Gal I mRNA. 1054 81

The ST6Gal I is a sialyltransferase that modifies N-linked oligosaccharides of glycoproteins. Previous results suggested a role for luminal stem and active domain sequences in the efficiency of ST6Gal I Golgi retention. Characterization of a series of STtyr isoform deletion mutants demonstrated that the stem is sensitive to proteases and that preventing cleavage in this region leads to increased cell surface expression. A mutant lacking amino acids 32-104 (STDelta4) is not active or cleaved and secreted like the wild type STtyr, but does exhibit increased cell surface expression. It is probable that the STDelta4 mutant lacks the stem region and some amino acids of the active domain because the STDelta5 mutant lacking amino acids 86-104 is also not active but is cleaved and secreted. In contrast, deletion of stem amino acids between residues 32 and 86 in the STDelta1, STDelta2, and STDelta3 mutants does not inactive these enzyme forms, eliminate their cleavage and secretion, or increase their cell surface expression. Surprisingly, cleavage occurs even though the previously identified Asn63-Ser 64 cleavage site is missing. Further evaluation demonstrated that a cleavage site between Lys 40 and Glu 41 is used in COS cells. Mutagenesis of Lys 40 significantly decreased, but did not eliminate cleavage, suggesting that there are additional secondary sites of cleavage in the ST6Gal I stem.
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PMID:The relationship between ST6Gal I Golgi retention and its cleavage-secretion. 1056 65

We have addressed the effects of estradiol and 4-OH-tamoxifen on the expression of five sialyltransferases in the hormono-dependent MCF-7 cell line using a Multiplex RT-PCR approach. Estradiol induced a statistically significant increase in ST3Gal III and a decrease in ST6Gal I, whereas the two other enzymes, ST3Gal IV and ST3Gal I, are not modified and expression of the fifth enzyme, ST3Gal II, was very low or not detectable. Estradiol effects were dose dependent and completely antagonized by 4OH-tamoxifen. In addition, there is no direct relation between cellular proliferation and sialyltransferase expression. This suggests that ST3Gal III and ST6Gal I could be used as supplementary markers of hormono-sensitivity in breast cancer.
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PMID:Regulation of sialyltransferase expression by estradiol and 4-OH-tamoxifen in the human breast cancer cell MCF-7. 1068 17

The ST6Gal I is a sialyltransferase that functions in the late Golgi to modify the N-linked oligosaccharides of glycoproteins. The ST6Gal I is expressed as two isoforms with a single amino acid difference in their catalytic domains. The STcys isoform is stably retained in the cell and is predominantly found in the Golgi, whereas the STtyr isoform is only transiently localized in the Golgi and is cleaved and secreted from a post-Golgi compartment. These two ST6Gal I isoforms were used to explore the role of the bilayer thickness mechanism and oligomerization in Golgi localization. Analysis of STcys and STtyr proteins with longer transmembrane regions suggested that the bilayer thickness mechanism is not the predominant mechanism used for ST6Gal I Golgi localization. In contrast, the formation and quantity of Triton X-100-insoluble oligomers was correlated with the stable or transient localization of the ST6Gal I isoforms in the Golgi. Nearly 100% of the STcys and only 13% of the STtyr were found as Triton-insoluble oligomers when Golgi membranes of COS-1 cells expressing these proteins were solubilized at pH 6.3, the pH of the late Golgi. In contrast, both proteins were found in the soluble fraction when these membranes were solubilized at pH 8.0. Analysis of other mutants suggested that a conformational change in the catalytic domain rather than increased disulfide bond-based cross-linking is the basis for the increased ability of STcys protein to form oligomers and the stable localization of STcys protein in the Golgi.
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PMID:Formation of insoluble oligomers correlates with ST6Gal I stable localization in the golgi. 1078 4

The effect of the various glycosyltransferases on glycosphingolipids was examined, using transfected swine endothelial cell (SEC) lines. The reactivity of parental SEC to normal human serum (NHS) and Griffonia simplicifolia IB(4) (GSIB4) lectin, which binds to the Gal alpha1-3 Gal beta 1-4 GlcNAc-R (alpha-galactosyl epitope), was reduced by approximately 20% by the treatment with D-PDMP (D-threo-1-phenyl-2-decan- oylamino-3-morpholino-1-propanol), suggesting that glycosphingolipids contained by SEC have a considerable amount of the alpha-galactosyl epitope. The overexpression of two different types of glycosyltransferase, N-acetylglucosaminyl transferase III (GnT-III), as well as alpha2, 6-sialyltransferase (ST6Gal I), alpha2,3-sialyltransferase (ST3Gal III), and alpha1,2-fucosyltransferase (alpha1,2FT), suppresses the total antigenicity of SEC significantly. However, the reduction in reactivities toward NHS and GSIB4 lectin in the case of GnT-III transfectants was milder than those in other transfectants. Western blot analysis indicated that the glycoproteins in all transfectants had diminished reactivity to NHS and GSIB4 lectin to approximately the same extent. Therefore, the neutral glycosphingolipids of these transfectants were separated by thin layer chromatography, followed by immunostaining with NHS and GSIB4 lectin. The levels of the alpha-galactosyl epitope in glycosphingolipids were not decreased in the GnT-III transfectants but were in the ST6Gal I, ST3Gal III, and alpha1,2FT transfectants. These data indicate that ST6Gal I, ST3Gal III, and alpha1,2FT reduced the alpha-galactosyl epitope in both glycoproteins and glycosphingolipids, while GnT-III reduced them only in glycoproteins.
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PMID:Reduction of the major xenoantigen on glycosphingolipids of swine endothelial cells by various glycosyltransferases. 1091 Sep 78


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