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St3gal5  -  ST3 beta-galactoside alpha-2,3...

Mus musculus

Synonyms: 3S-T, CMP-NeuAc:lactosylceramide alpha-2,3-sialyltransferase, GM3 synthase, GM3-specific sialytransferase, GM3S, ...
 
 
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Disease relevance of St3gal5

  • Furthermore, we verified that the ST3Gal-V mutant created using the SUNGA method maintains its high activity when expressed in Escherichia coli thereby establishing the usefulness of the SUNGA method in exploring the function of N-glycans in vivo [1].
  • GD1a could be considered as an IL-3-associated ganglioside and was expressed in a tight connection with a single glycosyltransferase (GM3 synthase) up-regulation and with IL-3 expression in murine myelogenous leukemia cells [2].
  • To investigate the significance of the ganglioside GM3 in cancer malignancy, we established GM3-reconstituted cells by transfecting the cDNA of GM3 synthase into a GM3-deficient subclone of the 3LL Lewis lung carcinoma cell line (Uemura, S. (2003) Glycobiology, 13, 207-216) [3].
 

High impact information on St3gal5

  • To determine the role of ganglioside synthesis within the CNS, mice carrying null mutations in two critical ganglioside-specific glycosyltransferase genes, Siat9 (encoding GM3 synthase) and Galgt1 (encoding GM2 synthase), were generated [4].
  • Similarly, when the newly cloned chicken GM3 synthase gene is transfected into v-Jun-transformed DF1 with the pcDNA vector, the GM3 synthase level is restored to that of control cells, and the ability of the cells to form agar colonies is reduced [5].
  • 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 [6].
  • Further, inhibition of GM3 synthase using specific SiRNA partially reversed the AGE effects on mesangial cell proliferation [6].
  • Using cerebellar granule cells obtained from GM3 synthase knock-out mice, we found that BoNT/C did not elicit a toxic effect but that BoNT/D still inhibited glutamate release to the same extent as in granule cells from wild type mice [7].
 

Chemical compound and disease context of St3gal5

 

Biological context of St3gal5

 

Anatomical context of St3gal5

 

Associations of St3gal5 with chemical compounds

  • The apparent Km value for LacCer was 9.3 microM. mST3Gal V did not exhibit any activity toward other substrates we tested in this study, including glycolipids, glycoproteins and disaccharides [9].
  • Moreover, introduction of pM1T-9 into L cell (lacking GM3 synthase), previously transfected with GM2/GD2 synthase gene, resulted in the definite expression of asialo-GM1 [14].
  • By examining mutants of mST3Gal-V, in which each asparagine was replaced with glutamine (N180Q, N224Q, N334Q), we determined that all three sites are N-glycosylated and that each N-glycan is required for enzyme activity [1].
  • In order to elucidate the biochemical mechanisms of these PDMP effects, the activities of GlcCer synthase, LacCer synthase, and GM3 synthase in B16 cell lysates were measured in the presence of PDMP [15].
  • Changes in the glycolipid composition and characteristic activation of GM3 synthase in the thymus of mouse after administration of dexamethasone [16].
 

Other interactions of St3gal5

  • Expression of the viral oncoprotein Jun (v-Jun) induces transformed cell clones with greatly reduced levels of GM3 and GM3 synthase (lactosylceramide alpha2,3-sialyltransferase) mRNA in both 10T1/2 and DF1 cell cultures [5].
  • Therefore, we considered whether the function in the activity that is performed in mST3Gal-V by the N-glycan could be substituted for by specific amino acid residues selected from the ST3Gal-V of other species or from related sialyltransferases (ST3Gal-I, -II, -III, and -IV), placed at or near the glycosylation sites [1].
  • Sp1 and AP2 enhance promoter activity of the mouse GM3-synthase gene [17].
  • The increased activity of Neu3 was paralleled by an increase of GM3 synthase mRNA and GM3 synthase activity [18].
  • To investigate the tissue distribution and subcellular localization of ST3GalV (CMP-NeuAc:lactosylceramide alpha2,3 sialyltransferase/GM3 synthase) in the adult mouse, we generated two antisera against mouse ST3GalV that were designated CS2 (directed against amino acids K227-I272) and CS14 (directed against amino acids D308-H359) [19].
 

Analytical, diagnostic and therapeutic context of St3gal5

References

  1. Substitution of the N-glycan function in glycosyltransferases by specific amino acids: ST3Gal-V as a model enzyme. Uemura, S., Kurose, T., Suzuki, T., Yoshida, S., Ito, M., Saito, M., Horiuchi, M., Inagaki, F., Igarashi, Y., Inokuchi, J. Glycobiology (2006) [Pubmed]
  2. Interleukin-3-associated expression of gangliosides in mouse myelogenous leukemia NFS60 cells introduced with interleukin-3 gene: expression of ganglioside GD1a and key involvement of CMP-NeuAc:lactosylceramide alpha 2-->3-sialyltransferase in GD1a expression. Tsunoda, A., Nakamura, M., Kirito, K., Hara, K., Saito, M. Biochemistry (1995) [Pubmed]
  3. Endogenously produced ganglioside GM3 endows etoposide and doxorubicin resistance by up-regulating Bcl-2 expression in 3LL Lewis lung carcinoma cells. Noguchi, M., Kabayama, K., Uemura, S., Kang, B.W., Saito, M., Igarashi, Y., Inokuchi, J. Glycobiology (2006) [Pubmed]
  4. Interruption of ganglioside synthesis produces central nervous system degeneration and altered axon-glial interactions. Yamashita, T., Wu, Y.P., Sandhoff, R., Werth, N., Mizukami, H., Ellis, J.M., Dupree, J.L., Geyer, R., Sandhoff, K., Proia, R.L. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  5. Reversion of the Jun-induced oncogenic phenotype by enhanced synthesis of sialosyllactosylceramide (GM3 ganglioside). Miura, Y., Kainuma, M., Jiang, H., Velasco, H., Vogt, P.K., Hakomori, S. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  6. 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]
  7. Binding of Clostridium botulinum type C and D neurotoxins to ganglioside and phospholipid. Novel insights into the receptor for clostridial neurotoxins. Tsukamoto, K., Kohda, T., Mukamoto, M., Takeuchi, K., Ihara, H., Saito, M., Kozaki, S. J. Biol. Chem. (2005) [Pubmed]
  8. Sialylation and sulfation of lactosylceramide distinctly regulate anchorage-independent growth, apoptosis, and gene expression in 3LL Lewis lung carcinoma cells. Uemura, S., Kabayama, K., Noguchi, M., Igarashi, Y., Inokuchi, J. Glycobiology (2003) [Pubmed]
  9. Molecular cloning and functional expression of a fifth-type alpha 2,3-sialyltransferase (mST3Gal V: GM3 synthase). Kono, M., Takashima, S., Liu, H., Inoue, M., Kojima, N., Lee, Y.C., Hamamoto, T., Tsuji, S. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  10. Molecular identification, tissue distribution and subcellular localization of mST3GalV/GM3 synthase. Stern, C.A., Braverman, T.R., Tiemeyer, M. Glycobiology (2000) [Pubmed]
  11. Expression cloning of mouse cDNA of CMP-NeuAc:Lactosylceramide alpha2,3-sialyltransferase, an enzyme that initiates the synthesis of gangliosides. Fukumoto, S., Miyazaki, H., Goto, G., Urano, T., Furukawa, K., Furukawa, K. J. Biol. Chem. (1999) [Pubmed]
  12. Developmental patterns of mST3GalV mRNA expression in the mouse: in situ hybridization using DIG-labeled RNA probes. Ji, M.Y., Lee, Y.C., Do, S., Nam, S.Y., Jung, K.Y., Kim, H.M., Park, L.K., Choo, Y.K. Arch. Pharm. Res. (2000) [Pubmed]
  13. Ganglioside GM3 participates in the pathological conditions of insulin resistance. Tagami, S., Inokuchi Ji, J., Kabayama, K., Yoshimura, H., Kitamura, F., Uemura, S., Ogawa, C., Ishii, A., Saito, M., Ohtsuka, Y., Sakaue, S., Igarashi, Y. J. Biol. Chem. (2002) [Pubmed]
  14. 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]
  15. Stimulation of glycosphingolipid biosynthesis by L-threo-1-phenyl-2-decanoylamino-1-propanol and its homologs in B16 melanoma cells. Inokuchi, J., Usuki, S., Jimbo, M. J. Biochem. (1995) [Pubmed]
  16. Changes in the glycolipid composition and characteristic activation of GM3 synthase in the thymus of mouse after administration of dexamethasone. Iwamori, M., Iwamori, Y. Glycoconj. J. (2005) [Pubmed]
  17. Sp1 and AP2 enhance promoter activity of the mouse GM3-synthase gene. Xia, T., Zeng, G., Gao, L., Yu, R.K. Gene (2005) [Pubmed]
  18. Plasma membrane production of ceramide from ganglioside GM3 in human fibroblasts. Valaperta, R., Chigorno, V., Basso, L., Prinetti, A., Bresciani, R., Preti, A., Miyagi, T., Sonnino, S. FASEB J. (2006) [Pubmed]
  19. A ganglioside-specific sialyltransferase localizes to axons and non-Golgi structures in neurons. Stern, C.A., Tiemeyer, M. J. Neurosci. (2001) [Pubmed]
  20. Combinatorial PCR approach to homology-based cloning: cloning and expression of mouse and human GM3-synthase. Kapitonov, D., Bieberich, E., Yu, R.K. Glycoconj. J. (1999) [Pubmed]
  21. Pathophysiological implication of ganglioside GM3 in early mouse embryonic development through apoptosis. Ju, E.J., Kwak, D.H., Lee, D.H., Kim, S.M., Kim, J.S., Kim, S.M., Choi, H.G., Jung, K.Y., Lee, S.U., Do, S.I., Park, Y.I., Choo, Y.K. Arch. Pharm. Res. (2005) [Pubmed]
 
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