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Gene Review

St8sia1  -  ST8 alpha-N-acetyl-neuraminide alpha-2,8...

Mus musculus

Synonyms: 9330109E03Rik, Alpha-2,8-sialyltransferase 8A, Alpha-N-acetylneuraminide alpha-2,8-sialyltransferase, GD3 synthase, GD3S, ...
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Disease relevance of St8sia1

  • GD3 synthase gene knockout mice exhibit thermal hyperalgesia and mechanical allodynia but decreased response to formalin-induced prolonged noxious stimulation [1].
  • Thus, the high GD2:GD3 ratios characteristic of most neuroblastomas result from low levels of GD3 synthase as well as high levels of GD2 synthase [2].
  • These results demonstrate that suppression of GD3-synthase expression, which results primarily in a marked decrease in the concentration of ganglioside GD3, greatly reduces cell spreading, invasion and both the incidence and growth rate of experimental metastasis of F-11 cells [3].

High impact information on St8sia1

  • In our previous study (G. Zeng et al., Biochemistry, 38: 8762-8769, 1999), we established a subclone of the rat dorsal root ganglion-derived F-11 cells in which the expression of ganglioside GD3 was inhibited by stable transfection of the antisense vector against CMP-NeuAc: GM3 alpha2-8 sialyltransferase (GD3-synthase) gene [4].
  • Therefore, our results demonstrate that reduced tumor growth in nude mice by suppression of GD3-synthase expression in F-11 cells results from minimal angiogenesis of the tumors through down-regulation of the VEGF expression, which indicates an important role for GD3 in tumor angiogenesis [4].
  • For example, in cell lines containing high amounts of GD2 ganglioside, the level of the preceding enzyme in the pathway (GD3 synthase) was unexpectedly low [2].
  • Results of the present study indicate that AGEs caused an inhibition of both bovine retinal pericyte (BRP) and rat renal mesangial cell (RMC) proliferation, associated with an increase of a-series gangliosides consecutive to GM3 synthase activity increase and GD3 synthase activity inhibition [5].
  • Furthermore, GD3 synthase gene expression strongly decreased MMP-9 promoter activity in response to TNF-alpha [6].

Biological context of St8sia1

  • Transfection of the protein A-fused ST8Sia III gene into COS-7 cells led to alpha 2,8-sialyltransferase activity toward sialylated glycoproteins and alpha 2,3-sialylated glycosphingolipids, such as alpha 2,3-sialylparagloboside and GM3 [7].
  • The predicted amino acid sequence of ST8Sia IV showed 15.2, 56.0, and 26% identity with those of so far cloned mouse alpha2,8-sialytransferases, i.e. GD3 synthase (ST8Sia I), STX(ST8Sia II), and Sia(alpha)2,3Galbeta1,4GlcNAc(alpha)2,8-sialyl-transferase (ST8Sia III) [8].
  • We generated double knock-out mice lacking the GM2/GD2 and the GD3 synthase gene by mating single gene mutants, and we analyzed the abnormal phenotypes of the mutant mice expressing only the GM3 ganglioside [9].
  • A cDNA clone of GD3 synthase, pD3T-31 was co-transfected with a cDNA library prepared from rat brain RNA using the pcDNAI expression vector [10].
  • When brain tissue was analyzed as a whole mass, a typical pattern corresponding to the reported findings obtained by biochemical analyses was observed, i.e., high expression of GD3 synthase gene in the early stage and gradual increase of GM2/GD2 synthase gene expression in the late stage of the development [11].

Anatomical context of St8sia1

  • Co-transfection of the cell line with pM1T-9 and a GD3 synthase cDNA resulted in the expression of GD1b as well as GM1 [10].
  • The mouse Sia alpha 2,3Gal beta 1, 4GalNAc alpha 2,8-sialyltransferase (ST8Sia III) genomic gene, whose transcripts are only expressed in fetal and newborn brain and testis, was isolated and its 5'-flanking region was analyzed [12].
  • However, on treatment with DMSO, which induces muscle cells, there was no change in the level of GD3 synthase activity, and its transcript was hardly detected during the course of muscle differentiation [13].
  • These results indicate that the GD3 synthase gene may be involved in early tooth development, particularly in the proliferation of dental epithelium [14].
  • In addition, dental epithelial cells transiently transfected with the GD3 synthase gene showed enhanced proliferation [14].

Associations of St8sia1 with chemical compounds

  • On the other hand, the level of GQ1b synthase (alpha 2,8-sialyltransferase, SAT-V) in RA-induced aggregates was significantly higher than that in neurons [13].
  • The cells that expressed GD3 were established from Neuro2a cells by transfection of a mammalian expression vector into which were carried a cDNA encoding GD3 synthase and the blasticidin-S-deaminase gene with a SV40 promoter, followed by selection with blasticidin-S-hydrochloride [15].
  • In addition, N2a-GD3 expressed acetylcholine esterase, indicating that the differentiation of Neuro2a cells was induced by expression of GD3 synthase and subsequent modification of the biosynthesis and expression of gangliosides [15].
  • In a search for the genes involved in this ganglioside-induced Neuro2a differentiation, we used a tetracycline-regulated GD3 synthase cDNA expression system combined with differential display PCRs to identify mRNAs that were differentially expressed at four representative time points during the process [16].
  • Optimum GD3 synthase activity was obtained at pH 6.0 using 0.1% detergent Triton CF-54 [17].

Regulatory relationships of St8sia1

  • Addition of neutralizing anti-Fas-L antibodies reduced the extent of 'low-K+'-induced apoptosis and abolished the increase in GD3 levels and GD3 synthase mRNA [18].

Other interactions of St8sia1


Analytical, diagnostic and therapeutic context of St8sia1


  1. GD3 synthase gene knockout mice exhibit thermal hyperalgesia and mechanical allodynia but decreased response to formalin-induced prolonged noxious stimulation. Handa, Y., Ozaki, N., Honda, T., Furukawa, K., Tomita, Y., Inoue, M., Furukawa, K., Okada, M., Sugiura, Y. Pain (2005) [Pubmed]
  2. Glycosylation pathways in the biosynthesis of gangliosides in melanoma and neuroblastoma cells: relative glycosyltransferase levels determine ganglioside patterns. Ruan, S., Lloyd, K.O. Cancer Res. (1992) [Pubmed]
  3. Reduced cell migration, tumor growth and experimental metastasis of rat F-11 cells whose expression of GD3-synthase is suppressed. Zeng, G., Gao, L., Yu, R.K. Int. J. Cancer (2000) [Pubmed]
  4. Suppression of ganglioside GD3 expression in a rat F-11 tumor cell line reduces tumor growth, angiogenesis, and vascular endothelial growth factor production. Zeng, G., Gao, L., Birklé, S., Yu, R.K. Cancer Res. (2000) [Pubmed]
  5. a-Series gangliosides mediate the effects of advanced glycation end products on pericyte and mesangial cell proliferation: a common mediator for retinal and renal microangiopathy? Masson, E., Troncy, L., Ruggiero, D., Wiernsperger, N., Lagarde, M., Bawab, S.E. Diabetes (2005) [Pubmed]
  6. Disialoganglioside (GD3) synthase gene expression suppresses vascular smooth muscle cell responses via the inhibition of ERK1/2 phosphorylation, cell cycle progression, and matrix metalloproteinase-9 expression. Moon, S.K., Kim, H.M., Lee, Y.C., Kim, C.H. J. Biol. Chem. (2004) [Pubmed]
  7. Molecular cloning of Sia alpha 2,3Gal beta 1,4GlcNAc alpha 2,8-sialyltransferase from mouse brain. Yoshida, Y., Kojima, N., Kurosawa, N., Hamamoto, T., Tsuji, S. J. Biol. Chem. (1995) [Pubmed]
  8. Molecular cloning and characterization of a third type of N-glycan alpha 2,8-sialyltransferase from mouse lung. Yoshida, Y., Kojima, N., Tsuji, S. J. Biochem. (1995) [Pubmed]
  9. Refractory skin injury in complex knock-out mice expressing only the GM3 ganglioside. Inoue, M., Fujii, Y., Furukawa, K., Okada, M., Okumura, K., Hayakawa, T., Furukawa, K., Sugiura, Y. J. Biol. Chem. (2002) [Pubmed]
  10. Expression cloning of rat cDNA encoding UDP-galactose:GD2 beta1,3-galactosyltransferase that determines the expression of GD1b/GM1/GA1. Miyazaki, H., Fukumoto, S., Okada, M., Hasegawa, T., Furukawa, K. J. Biol. Chem. (1997) [Pubmed]
  11. Heterogeneity in the expression pattern of two ganglioside synthase genes during mouse brain development. Yamamoto, A., Haraguchi, M., Yamashiro, S., Fukumoto, S., Furukawa, K., Takamiya, K., Atsuta, M., Shiku, H., Furukawa, K. J. Neurochem. (1996) [Pubmed]
  12. Unique genomic structure and expression of the mouse alpha 2,8-sialyltransferase (ST8Sia III) gene. Yoshida, Y., Kurosawa, N., Kanematsu, T., Taguchi, A., Arita, M., Kojima, N., Tsuji, S. Glycobiology (1996) [Pubmed]
  13. Glycolipid sialyltransferases are enhanced during neural differentiation of mouse embryonic carcinoma cells, P19. Osanai, T., Watanabe, Y., Sanai, Y. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  14. GD3 synthase gene found expressed in dental epithelium and shown to regulate cell proliferation. Yamada, A., Fukumoto, E., Kamasaki, Y., Ida-Yonemochi, H., Saku, T., Fujiwara, T., Fukumoto, S. Arch. Oral Biol. (2005) [Pubmed]
  15. Induction of cholinergic differentiation with neurite sprouting by de novo biosynthesis and expression of GD3 and b-series gangliosides in Neuro2a cells. Kojima, N., Kurosawa, N., Nishi, T., Hanai, N., Tsuji, S. J. Biol. Chem. (1994) [Pubmed]
  16. Isolation of 10 differentially expressed cDNAs in differentiated Neuro2a cells induced through controlled expression of the GD3 synthase gene. Liu, H., Nakagawa, T., Kanematsu, T., Uchida, T., Tsuji, S. J. Neurochem. (1999) [Pubmed]
  17. Ganglioside GD3 biosynthesis in normal and mutant mouse embryos. Novikov, A.M., Seyfried, T.N. Biochem. Genet. (1991) [Pubmed]
  18. Activation of Fas receptor is required for the increased formation of the disialoganglioside GD3 in cultured cerebellar granule cells committed to apoptotic death. Castiglione, M., Spinsanti, P., Iacovelli, L., Lenti, L., Martini, F., Gradini, R., Di Giorgi Gerevini, V., Caricasole, A., Caruso, A., De Maria, R., Nicoletti, F., Melchiorri, D. Neuroscience (2004) [Pubmed]
  19. Mice expressing only monosialoganglioside GM3 exhibit lethal audiogenic seizures. Kawai, H., Allende, M.L., Wada, R., Kono, M., Sango, K., Deng, C., Miyakawa, T., Crawley, J.N., Werth, N., Bierfreund, U., Sandhoff, K., Proia, R.L. J. Biol. Chem. (2001) [Pubmed]
  20. Molecular cloning and expression of a sixth type of alpha 2,8-sialyltransferase (ST8Sia VI) that sialylates O-glycans. Takashima, S., Ishida, H.K., Inazu, T., Ando, T., Ishida, H., Kiso, M., Tsuji, S., Tsujimoto, M. J. Biol. Chem. (2002) [Pubmed]
  21. Chromosome mapping of the GD3 synthase gene (SIAT8) in human and mouse. Matsuda, Y., Nara, K., Watanabe, Y., Saito, T., Sanai, Y. Genomics (1996) [Pubmed]
  22. Molecular cloning of cDNA for rat brain GD3-synthase. Zeng, G., Gao, L., Ariga, T., Yu, R.K. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
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