Disease relevance of St6gal1

• Secretion of ST6Gal I from the liver into the plasma is known to be up-regulated during the acute-phase response [1].
• The relative extent of exogenous sialyltransferase-mediated sialylation (per cellular protein) was thymocytes greater than T-cells greater than T-cell lymphoma (EL-4) greater than B-cells greater than B-cell lymphoma (AKTB-1b) greater than splenocytes [2].
• Alterations in surface glycoproteins and level of sialyltransferase of cells transformed by a temperature-sensitive mutant of simian virus 40 [3].
• A correlation between cell surface sialyltransferase, sialic acid, and glycosidase activities and the implantability of B16 murine melanoma [4].
• Therefore, the effect of a sialyltransferase inhibitor, 5-fluoro-2',3'-isopropylidene-5'-O-(4-N-acetyl-2,4-dideoxy-3,6,7,8-tetra -O -acetyl-1-methoxycarbonyl-D-glycero-alpha-D-galactooctapyranosyl)u ridine (Kl-8110), on the experimental lung metastasis of NL-17 or NL-44 cells was examined [5].

High impact information on St6gal1

• Here we report that mice deficient in both CD22 and its ligand (Cd22-/- St6gal1-/- mice) showed restored B cell receptor (BCR) signaling, suggesting that the suppressed signaling of St6gal1-/- cells is mediated through CD22 [6].
• Coincident with suppressed BCR signaling, B cells lacking ST6Gal I showed a net redistribution of the BCR to clathrin-rich microdomains containing most of the CD22, resulting in a twofold increase in the localization of CD22 together with the BCR [6].
• Sialyltransferase ST3Gal-IV operates as a dominant modifier of hemostasis by concealing asialoglycoprotein receptor ligands [7].
• Deficiency of ST6Gal was further found to alter phosphotyrosine accumulation during signal transduction from the B lymphocyte antigen receptor [8].
• When the levels of glycoprotein glycosyltransferases of the cells were examined, the level of sialyltransferase (CMP-N-acetylneuraminytransferase,EC 2.4.99.1) of the cells grown at the restrictive temperature was low compared with that of cells grown at the permissive temperature [3].

Chemical compound and disease context of St6gal1

• Correlation of retinoic acid-enhanced sialyltransferase activity and glycosylation of specific cell surface sialoglycoproteins with growth inhibition in a murine melanoma cell system [9].
• Reduction in cell membrane sialylation in the alpha 1,3GT gene-transfected melanoma cells is probably due to the competition between alpha 1,3GT with alpha 2,3 sialyltransferase or alha 2,6 sialyltransferase for the common acceptor N-acetyllactosamine in the Golgi apparatus [10].
• Retinoic acid (RA) treatment of murine S91-C2 melanoma cells has been found to augment the activity of glycoprotein: sialyltransferase in a dose-dependent and time-dependent process [11].

Biological context of St6gal1

• On the other hand, ST6Gal I, which has been known as the sole member of the ST6Gal-family for more than ten years, exhibited broad substrate specificity toward oligosaccharides, glycoproteins, and a glycolipid, paragloboside [12].
• The predicted amino acid sequence is 57.4% identical to the chick ST6GalNAc II sequence but 33.8% identical to the chick ST6GalNA I (GalNAc alpha2, 6-sialyltransferase) sequence [13].
• Characterization of 5'-flanking genomic regions indicated that the Galbeta1,3GalNAc-specific GalNAc alpha2,6-sialyltransferase promoter is embedded in a G+C-rich domain and contains no TATA or CAAT box but has putative binding sites for transcription factors Sp1 and AP-2 [13].
• This gene contained a 1590 bp open reading frame divided in five exons and the deduced amino-acid sequence didn't correspond to any sialyltransferase already known in other species [14].
• 5'-Rapid amplification of cDNA ends analysis demonstrated that the increase in ST6Gal I mRNA upon H-RasV12 or K-RasS12 transfection is mediated by the Siat1 housekeeping promoter P3-associated 5' untranslated exons [15].

Anatomical context of St6gal1

• Differential expression of mRNAs for sialyltransferase isoenzymes induced in the hippocampus of mouse following kindled seizures [16].
• Each of the four enzymes was expressed in COS-7 cells as a recombinant enzyme fused with protein A, and applied on an IgG-Sepharose gel to eliminate endogenous sialyltransferase activity [17].
• Highly selective losses of 9-O-acetylation of sialic acid residues were also observed, with ST6Gal-I deficiency causing loss on endothelium and ST3Gal-I deficiency giving a marked decrease on CD4(+) lymphocytes [18].
• As for the structures synthesized by the enzyme, the increase of ST6Gal I activity in the serum as well as in liver microsomes of the transgenic mice followed tumor progression [19].
• The sialyltransferase ST3Gal-I is not required for regulation of CD8-class I MHC binding during T cell development [20].

Associations of St6gal1 with chemical compounds

• Genetically altered mice with different sialyltransferase deficiencies show tissue-specific alterations in sialylation and sialic acid 9-O-acetylation [18].
• We previously reported that BACE1 cleaved rat beta-galactoside alpha2,6-sialyltransferase (ST6Gal I) that was overexpressed in COS cells and that the NH(2) terminus of ST6Gal I secreted from the cells (E41 form) was Glu(41) [1].
• This general increase in alpha2,6 sialylation on all glycoproteins is due to the increased activity of the galactoside:alpha2,6 sialyltransferase (ST6Gal I), which specifically transfers Neu5Ac residues in alpha2,6 linkage to Gal beta1,4GlcNAc units on N-glycans [19].
• The identity of this enzyme was confirmed by construction of a recombinant sialyltransferase in which the NH2-terminal part including the cytoplasmic tail, signal-anchor domain and stem region was replaced with an immuno-globulin signal sequence [21].
• Enzymatic assays indicate that the best acceptor substrate of ST6Gal II was the free disaccharide Galbeta1-4GlcNAc structure whereas ST6Gal I preferred Galbeta1-4GlcNAc-R disaccharide sequence linked to a protein [14].

Other interactions of St6gal1

• Here we examine the cell type-specific expression of terminal glycans in tissues of normal mice in comparison with animals deficient in ST6Gal-I (transfers alpha2-6-linked sialic acid to Galbeta1-4GlcNAc) or ST3Gal-I (transfers alpha2-3-linked sialic acid to Galbeta1-3GalNAc) [18].
• Recombinant ST6Gal II exhibited alpha2,6-sialyltransferase activity toward oligosaccharides that have the Galbeta1,4GlcNAc sequence at the nonreducing end of their carbohydrate groups, but it exhibited relatively low and no activity toward some glycoproteins and glycolipids, respectively [12].
• Mouse gene knockout studies have provided unimpeachable evidence of immune-relevant functions for several sialyltransferase enzymes including ST6Gal I, ST3Gal I, and ST3Gal IV [22].
• In particular, transfection of codon 12 point mutated H-Ras increases CMP-Neu5Ac: Galbeta1,4GlcNAc alpha2,6-sialyltransferase I (ST6Gal I) activity in rodent fibroblasts [15].
• We have disrupted the gene encoding GD3 synthase (GD3S), a sialyltransferase expressed in the CNS that is responsible for the synthesis of b-series gangliosides [23].

Analytical, diagnostic and therapeutic context of St6gal1

• We have investigated mice that lack ST6Gal and report that they are viable, yet exhibit hallmarks of severe immunosuppression unlike CD22-deficient mice [8].
• Using a rat ST6Gal I cDNA as a probe, Northern blots of total RNA extracted from the livers of control and transgenic mice revealed an increased (4-fold) expression of the ST6Gal I gene [19].
• Molecular cloning and genomic analysis of mouse Galbeta1, 3GalNAc-specific GalNAc alpha2,6-sialyltransferase [13].
• Quantitative analysis of expression of mouse sialyltransferase genes by competitive PCR [24].
• Multiple sequence alignment and subsequent phylogenic analysis showed that this new enzyme belonged to the ST6Gal subfamily and shared 48% identity with hST6Gal-I [14].

References