ST8SIA1

Summary

Gene Symbol: ST8SIA1
Description: ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1
Alias: GD3S, SIAT8, SIAT8-A, SIAT8A, ST8SiaI, alpha-N-acetylneuraminide alpha-2,8-sialyltransferase, ST8 alpha-N-acetylneuraminate alpha-2,8-sialyltransferase 1, alpha-2,8-sialyltransferase 8A, disialoganglioside (GD3) synthase, ganglioside GD3 synthase, ganglioside GT3 synthase, ganglioside-specific alpha-2,8-polysialyltransferase, sialyltransferase 8 (alpha-N-acetylneuraminate: alpha-2,8-sialytransferase, GD3 synthase) A, sialyltransferase 8A (alpha-N-acetylneuraminate: alpha-2,8-sialyltransferase, GD3 synthase), sialyltransferase St8Sia I, sialytransferase St8Sia I
Species: human
Products:     ST8SIA1

Top Publications

  1. Nara K, Watanabe Y, Maruyama K, Kasahara K, Nagai Y, Sanai Y. Expression cloning of a CMP-NeuAc:NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1'Cer alpha 2,8-sialyltransferase (GD3 synthase) from human melanoma cells. Proc Natl Acad Sci U S A. 1994;91:7952-6 pubmed
    ..The cDNA hybridized to a single mRNA species of 2.4 kb in melanoma cells. This sialyltransferase is distinctive in catalyzing the formation of the alpha 2-8 linkage of sialic acids. ..
  2. Matsuda Y, Nara K, Watanabe Y, Saito T, Sanai Y. Chromosome mapping of the GD3 synthase gene (SIAT8) in human and mouse. Genomics. 1996;32:137-9 pubmed
    ..The chromosomal location of the GD3 synthase gene (SIAT8) was determined in human and mouse using fluorescence in situ hybridization and interspecific backcross analysis, ..
  3. De Maria R, Lenti L, Malisan F, D Agostino F, Tomassini B, Zeuner A, et al. Requirement for GD3 ganglioside in CD95- and ceramide-induced apoptosis. Science. 1997;277:1652-5 pubmed
    ..Thus, GD3 ganglioside mediates the propagation of CD95-generated apoptotic signals in hematopoietic cells. ..
  4. Dhanushkodi A, Xue Y, Roguski E, Ding Y, Matta S, Heck D, et al. Lentiviral-mediated knock-down of GD3 synthase protects against MPTP-induced motor deficits and neurodegeneration. Neurosci Lett. 2019;692:53-63 pubmed publisher
    ..We recently reported that targeted deletion of St8sia1, the gene that codes for GD3S, prevents motor impairments and significantly attenuates neurodegeneration induced ..
  5. Momma D, Onodera T, Homan K, Matsubara S, Sasazawa F, Furukawa J, et al. Coordinated existence of multiple gangliosides is required for cartilage metabolism. Osteoarthritis Cartilage. 2019;27:314-325 pubmed publisher
    ..GalNAcT) gene, which encodes an enzyme of major gangliosides synthesis, and the GD3 synthase (GD3S) gene, which encodes an enzyme of partial gangliosides synthesis...
  6. Nguyen K, Yan Y, Yuan B, Dasgupta A, Sun J, Mu H, et al. ST8SIA1 Regulates Tumor Growth and Metastasis in TNBC by Activating the FAK-AKT-mTOR Signaling Pathway. Mol Cancer Ther. 2018;17:2689-2701 pubmed publisher
    ..We have recently discovered that ganglioside GD2 expression defines BCSCs and that ST8SIA1 regulates GD2 expression and BCSC function...
  7. Wang J, Cheng A, Wakade C, Yu R. Ganglioside GD3 is required for neurogenesis and long-term maintenance of neural stem cells in the postnatal mouse brain. J Neurosci. 2014;34:13790-800 pubmed publisher
    ..Here, we investigated its role in postnatal and adult neurogenesis in GD3-synthase knock-out (GD3S-KO) and wild-type mice...
  8. Hsu F, Shapiro M, Chen M, McWilliams D, Seaburg L, Tangen S, et al. Immature recent thymic emigrants are eliminated by complement. J Immunol. 2014;193:6005-15 pubmed publisher
    ..that the defect in sialylation is due to aberrant α2,8-linked sialylation, and the expression of three genes (ST8sia1, ST8sia4, and ST8sia6) that mediate α2,8 sialylation are downregulated in NKAP-defcient RTEs...
  9. Ji S, Ohkawa Y, Tokizane K, Ohmi Y, Banno R, Furukawa K, et al. b-Series gangliosides crucially regulate leptin secretion in adipose tissues. Biochem Biophys Res Commun. 2015;459:189-195 pubmed publisher
    ..Expression analysis of leptin revealed that leptin accumulated in the adipose tissues of GD3 synthase-knockout (GD3S KO) mice...

More Information

Publications54

  1. Kozaki Y, Umetsu R, Mizukami Y, Yamamura A, Kitamori K, Tsuchikura S, et al. Peripheral gene expression profile of mechanical hyperalgesia induced by repeated cold stress in SHRSP5/Dmcr rats. J Physiol Sci. 2015;65:417-25 pubmed publisher
    ..We found significantly changed expression in eight pain-related genes (upregulated: Fyn, St8sia1, and Tac 1; downregulated: Ctsb, Fstl1, Itpr1, Npy, S100a10)...
  2. Sumantran V, Mishra P, Sudhakar N. Microarray analysis of differentially expressed genes regulating lipid metabolism during melanoma progression. Indian J Biochem Biophys. 2015;52:125-31 pubmed
    ..Genes for synthesis of pro-tumorigenic GM3 and GD3 gangliosides (UGCG, HEXA, ST3GAL5 and ST8SIA1) were also upregulated in melanoma...
  3. Dorrell C, Schug J, Canaday P, Russ H, Tarlow B, Grompe M, et al. Human islets contain four distinct subtypes of ? cells. Nat Commun. 2016;7:11756 pubmed publisher
    ..subtypes of human ? cells, which we refer to as ?1-4, and which are distinguished by differential expression of ST8SIA1 and CD9...
  4. Akkhawattanangkul Y, Maiti P, Xue Y, Aryal D, Wetsel W, Hamilton D, et al. Targeted deletion of GD3 synthase protects against MPTP-induced neurodegeneration. Genes Brain Behav. 2017;16:522-536 pubmed publisher
    ..GM1 ganglioside and decrease the pro-apoptotic GD3 ganglioside - such as inhibition of GD3 synthase (GD3S) or administration of sialidase - are neuroprotective in vitro and in a number of preclinical models...
  5. Nel M, Jalali Sefid Dashti M, Gamieldien J, Heckmann J. Exome sequencing identifies targets in the treatment-resistant ophthalmoplegic subphenotype of myasthenia gravis. Neuromuscul Disord. 2017;27:816-825 pubmed publisher
    ..014) and SPTLC3insACAC (p = 0.055) with OP-MG, but ST8SIA1delCCC could not be verified by Sanger sequencing...
  6. Eby J, Barse L, Henning S, Rabelink M, Klarquist J, Gilbert E, et al. Alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1 can support immune responses toward tumors overexpressing ganglioside D3 in mice. Cancer Immunol Immunother. 2017;66:63-75 pubmed publisher
    ..We show that DNA encoding ?-N-acetyl-neuraminide ?-2,8-sialyltransferase 1 (SIAT8) introduced by gene gun vaccination in vivo leads to overexpression of GD3 and delays tumor growth...
  7. Ji S, Tokizane K, Ohkawa Y, Ohmi Y, Banno R, Okajima T, et al. Increased a-series gangliosides positively regulate leptin/Ob receptor-mediated signals in hypothalamus of GD3 synthase-deficient mice. Biochem Biophys Res Commun. 2016;479:453-460 pubmed publisher
    ..However, little is known about their roles in adipose tissues and hypothalamus. In GD3 synthase-knockout (GD3S KO) mice, deletion of b-series gangliosides resulted in the reduction of serum leptin due to disturbed secretion ..
  8. Kwon K, Chung T, Kwak C, Choi H, Kim K, Ha S, et al. Disialyl GD2 ganglioside suppresses ICAM-1-mediated invasiveness in human breast cancer MDA-MB231 cells. Int J Biol Sci. 2017;13:265-275 pubmed publisher
    ..i>In vitro invasion potentials of the GD3 synthase over-expressing cells (pc3-GD3s) were significantly suppressed when compared with control cells...
  9. Liang Y, Wang C, Wang I, Chen Y, Li L, Lin C, et al. Interaction of glycosphingolipids GD3 and GD2 with growth factor receptors maintains breast cancer stem cell phenotype. Oncotarget. 2017;8:47454-47473 pubmed publisher
    ..in approximately half of all invasive ductal breast carcinoma cases, and enhanced expression of GD3 synthase (GD3S, alpha-N-acetylneuraminide alpha-2,8-sialyltransferase) in estrogen receptor-negative breast tumors, was shown to ..
  10. Furukawa K, Ohmi Y, Ji S, Zhang P, Bhuiyan R, Ohkawa Y, et al. Glycolipids: Essential regulator of neuro-inflammation, metabolism and gliomagenesis. Biochim Biophys Acta Gen Subj. 2017;1861:2479-2484 pubmed publisher
    ..From study of gene knockout mice of St8sia1, new roles of b-series gangliosides in leptin secretion from adipocytes, and roles of a-series gangliosides in ..
  11. Shan Y, Liu Y, Zhao L, Liu B, Li Y, Jia L. MicroRNA-33a and let-7e inhibit human colorectal cancer progression by targeting ST8SIA1. Int J Biochem Cell Biol. 2017;90:48-58 pubmed publisher
    ..b>ST8SIA1 was highly expressed in CRC tissues and HCT-8/5-FU cells, which was negatively correlated with miR-33a/let-7e ..
  12. Husain S, Yildirim Toruner C, Rubio J, Field J, Schwalb M, Cook S, et al. Variants of ST8SIA1 are associated with risk of developing multiple sclerosis. PLoS ONE. 2008;3:e2653 pubmed publisher
    ..Here we present two independent studies supporting an allelic association of MS with polymorphisms in the ST8SIA1 gene, located on chromosome 12p12 and encoding ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1...
  13. Tomassini B, Malisan F, Franchi L, Nicolò C, Calvo G, Saito T, et al. Calnexin suppresses GD3 synthase-induced apoptosis. FASEB J. 2004;18:1553-5 pubmed
    ..Reconstitution of calnexin confers protection to deficient cells. Thus, calnexin controls the biological outcome of GD3 accumulation and reveals a novel role in the stress response. ..
  14. Ha K, Lee Y, Kim C. Overexpression of GD3 synthase induces apoptosis of vascular endothelial ECV304 cells through downregulation of Bcl-2. FEBS Lett. 2004;568:183-7 pubmed
    ..Therefore, we conclude that GD3 synthase has an apoptotic effect on ECV304 cells through downregulation of Bcl-2 expression via dephosphorylation of AKT and CREB. ..
  15. Park H, Kim J, Yoon J, Choi Y, Choi Y, Kook K, et al. Identification and Functional Characterization of ST3GAL5 and ST8SIA1 Variants in Patients with Thyroid-Associated Ophthalmopathy. Yonsei Med J. 2017;58:1160-1169 pubmed publisher
    This study was conducted to identify and to functionally characterize genetic variants in ST3GAL5 and ST8SIA1 in Korean patients with thyroid-associated ophthalmopathy (TAO)...
  16. Mandal C, Sarkar S, Chatterjee U, Schwartz Albiez R, Mandal C. Disialoganglioside GD3-synthase over expression inhibits survival and angiogenesis of pancreatic cancer cells through cell cycle arrest at S-phase and disruption of integrin-?1-mediated anchorage. Int J Biochem Cell Biol. 2014;53:162-73 pubmed publisher
    ..Taken together, our study provides support for the GD3-induced cell cycle arrest, disruption of integrin-?1-mediated anchorage, inhibition of angiogenesis and thereby induced apoptosis in pancreatic cancer cells. ..
  17. Steenackers A, Vanbeselaere J, Cazet A, Bobowski M, Rombouts Y, Colomb F, et al. Accumulation of unusual gangliosides G(Q3) and G(P3) in breast cancer cells expressing the G(D3) synthase. Molecules. 2012;17:9559-72 pubmed publisher
    ..ST8Sia I in MCF-7 breast cancer cells and analyzed the glycosphingolipid composition of wild type (WT) and GD3S+ clones...
  18. Miyata M, Ichihara M, Tajima O, Sobue S, Kambe M, Sugiura K, et al. UVB-irradiated keratinocytes induce melanoma-associated ganglioside GD3 synthase gene in melanocytes via secretion of tumor necrosis factor ? and interleukin 6. Biochem Biophys Res Commun. 2014;445:504-10 pubmed publisher
  19. Haraguchi M, Yamashiro S, Yamamoto A, Takamiya K, Lloyd K, Shiku H, et al. Isolation of GD3 synthase gene by expression cloning of GM3 alpha-2,8-sialyltransferase cDNA using anti-GD2 monoclonal antibody. Proc Natl Acad Sci U S A. 1994;91:10455-9 pubmed
    For the isolation of ganglioside GD3 synthase (EC 2.4.99.8) cDNA, we developed an expression cloning approach that used an anti-GD2 monoclonal antibody for selection...
  20. Chumpen Ramirez S, Ruggiero F, Daniotti J, Valdez Taubas J. Ganglioside glycosyltransferases are S-acylated at conserved cysteine residues involved in homodimerisation. Biochem J. 2017;474:2803-2816 pubmed publisher
    ..We observed an increase in ST3Gal-II dimers in the presence of the PAT inhibitor 2-bromopalmitate, suggesting that GT homodimerisation may be regulating S-acylation. ..
  21. Sarkar T, Battula V, Werden S, Vijay G, Ramirez Peña E, Taube J, et al. GD3 synthase regulates epithelial-mesenchymal transition and metastasis in breast cancer. Oncogene. 2015;34:2958-67 pubmed publisher
    ..Moreover, we found that GD3 synthase (GD3S)--an enzyme involved in GD2 biosynthesis--is critical for GD2 production and could serve as a potential druggable ..
  22. Chalasani N, Guo X, Loomba R, Goodarzi M, Haritunians T, Kwon S, et al. Genome-wide association study identifies variants associated with histologic features of nonalcoholic Fatty liver disease. Gastroenterology. 2010;139:1567-76, 1576.e1-6 pubmed publisher
    ..A GWAS significantly associated genetic variants with features of hepatic histology in patients with NAFLD. These findings should be validated in larger and more diverse cohorts. ..
  23. Kang N, Kang Y, Kang S, Lee Y, Choi H, Lee Y, et al. Transcriptional regulation of the human GD3 synthase gene expression in Fas-induced Jurkat T cells: a critical role of transcription factor NF-kappaB in regulated expression. Glycobiology. 2006;16:375-89 pubmed
    ..In addition, the translocation of NF-kappaB-binding protein to nucleus by Fas activation is also crucial for the increased expression of the GD3 synthase gene in Fas-activated Jurkat T cells. ..
  24. Kang N, Kim C, Kim K, Ko J, Lee J, Jeong Y, et al. Expression of the human CMP-NeuAc:GM3 alpha2,8-sialyltransferase (GD3 synthase) gene through the NF-kappaB activation in human melanoma SK-MEL-2 cells. Biochim Biophys Acta. 2007;1769:622-30 pubmed
    ..These results indicate that NF-kappaB plays an essential role in the transcriptional activity of human GD3 synthase gene essential for GD3 synthesis in SK-MEL-2 cells. ..
  25. Kang S, Kim Y, Kong Y, Song K, Chang Y, Park Y, et al. Disialoganglioside GD3 synthase expression recruits membrane transglutaminase 2 during erythroid differentiation of the human chronic myelogenous leukemia K562 cells. Proteomics. 2008;8:3317-28 pubmed publisher
    ..Finally, GD3 synthase-transfected cells accelerated the erythroid differentiation. Therefore, we propose that the recruitment of TG2 into membranes by GD3 might play an important role in the erythroid differentiation in K562 cells. ..
  26. Teintenier Lelièvre M, Julien S, Juliant S, Guerardel Y, Duonor Cérutti M, Delannoy P, et al. Molecular cloning and expression of a human hST8Sia VI (alpha2,8-sialyltransferase) responsible for the synthesis of the diSia motif on O-glycosylproteins. Biochem J. 2005;392:665-74 pubmed
  27. Ramagopalan S, Morrison K, Para A, Handel A, Disanto G, Handunnetthi L, et al. Variants in ST8SIA1 do not play a major role in susceptibility to multiple sclerosis in Canadian families. J Neuroimmunol. 2009;212:142-4 pubmed publisher
    Multiple sclerosis (MS) is a complex trait with a significant genetic component. Recent work has implicated the ST8SIA1 gene, encoding a ganglioside synthase, in susceptibility to the disease, perhaps with a parent-of-origin effect...
  28. Cazet A, Groux Degroote S, Teylaert B, Kwon K, Lehoux S, Slomianny C, et al. GD3 synthase overexpression enhances proliferation and migration of MDA-MB-231 breast cancer cells. Biol Chem. 2009;390:601-9 pubmed publisher
    ..This suggests that G(D3) synthase overexpression may contribute to increasing the malignant properties of breast cancer cells. ..
  29. Dae H, Kwon H, Kang N, Song N, Kim K, Kim C, et al. Isolation and functional analysis of the human glioblastoma-specific promoter region of the human GD3 synthase (hST8Sia I) gene. Acta Biochim Biophys Sin (Shanghai). 2009;41:237-45 pubmed
    ..These results indicated that both AREB6 and Elk-1 might play an essential role in the transcriptional activity of hST8Sia I gene essential for GD3 synthesis in human glioblastoma cells. ..
  30. Gu Y, Yu R. Identification and analysis of novel functional sites in human GD3-synthase. Biochem Biophys Res Commun. 2008;370:67-71 pubmed publisher
  31. Rentería M, Coolen M, Statham A, Choi R, Qu W, Campbell M, et al. GWAS of DNA methylation variation within imprinting control regions suggests parent-of-origin association. Twin Res Hum Genet. 2013;16:767-81 pubmed publisher
    ..Nevertheless, these associations will require future experimental validation or replication in larger and independent samples. ..
  32. Ko K, Takahashi T, Urano T, Sanai Y, Nagino M, Nimura Y, et al. Fundamental study of small interfering RNAs for ganglioside GD3 synthase gene as a therapeutic target of lung cancers. Oncogene. 2006;25:6924-35 pubmed
    ..These results suggested that siRNAs and/or RNAi expression vectors to generate siRNAs are promising approach to overcome human lung cancers. ..
  33. Furukawa K, Horie M, Okutomi K, Sugano S, Furukawa K. Isolation and functional analysis of the melanoma specific promoter region of human GD3 synthase gene. Biochim Biophys Acta. 2003;1627:71-8 pubmed
    ..They also commonly contained a GT/CG repeat sequence at upstream of -1200 approximately -1300 nt, suggesting that they form Z-type DNA, and are involved in the gene regulation. ..
  34. Nakayama J, Fukuda M, Hirabayashi Y, Kanamori A, Sasaki K, Nishi T, et al. Expression cloning of a human GT3 synthase. GD3 AND GT3 are synthesized by a single enzyme. J Biol Chem. 1996;271:3684-91 pubmed
    ..Taken together, these results indicate that C series polysialogangliosides are synthesized by a ganglioside-specific polysialyltransferase, GD3/GT3ST, that is specifically expressed in neural tissues. ..
  35. Mandelli L, Emiliani R, Porcelli S, Fabbri C, Albani D, Serretti A. Genes involved in neuroplasticity and stressful life events act on the short-term response to antidepressant treatment: a complex interplay between genetics and environment. Hum Psychopharmacol. 2014;29:388-91 pubmed publisher
  36. Sasaki K, Kurata K, Kojima N, Kurosawa N, Ohta S, Hanai N, et al. Expression cloning of a GM3-specific alpha-2,8-sialyltransferase (GD3 synthase). J Biol Chem. 1994;269:15950-6 pubmed
    ..The deduced primary sequence also contains the "sialyl motif" conserved among all the sialyltransferases cloned to date. The polymerase chain reaction analysis reveals that this gene is located on chromosome 12. ..
  37. Sasaki K, Watanabe E, Kawashima K, Sekine S, Dohi T, Oshima M, et al. Expression cloning of a novel Gal beta (1-3/1-4) GlcNAc alpha 2,3-sialyltransferase using lectin resistance selection. J Biol Chem. 1993;268:22782-7 pubmed
    ..The cloning approach based on lectin resistance may be useful for the isolation of cDNAs encoding other mammalian glycosyltransferases. ..
  38. Cazet A, Lefebvre J, Adriaenssens E, Julien S, Bobowski M, Grigoriadis A, et al. GD? synthase expression enhances proliferation and tumor growth of MDA-MB-231 breast cancer cells through c-Met activation. Mol Cancer Res. 2010;8:1526-35 pubmed publisher
    ..G(D3) is overexpressed in ?50% of invasive ductal breast carcinoma, and the G(D3) synthase gene (ST8SIA1) displays higher expression among estrogen receptor-negative breast cancer tumors, associated with a decreased ..
  39. Yeh S, Wang P, Lou Y, Khoo K, Hsiao M, Hsu T, et al. Glycolipid GD3 and GD3 synthase are key drivers for glioblastoma stem cells and tumorigenicity. Proc Natl Acad Sci U S A. 2016;113:5592-7 pubmed publisher
    ..Furthermore, GD3 synthase (GD3S) is increased in neurospheres and human GBM tissues, but not in normal brain tissues, and suppression of GD3S ..
  40. Ruckhäberle E, Karn T, Rody A, Hanker L, Gätje R, Metzler D, et al. Gene expression of ceramide kinase, galactosyl ceramide synthase and ganglioside GD3 synthase is associated with prognosis in breast cancer. J Cancer Res Clin Oncol. 2009;135:1005-13 pubmed publisher
    ..in expression of ceramide galactosyl transferase (UGT8), ceramide kinase (CERK), and Ganglioside GD3-Synthase (ST8SIA1) in breast cancer cells were investigated by using microarray data of 1,581 tumor samples...
  41. Lluis J, Llacuna L, von Montfort C, Bárcena C, Enrich C, Morales A, et al. GD3 synthase overexpression sensitizes hepatocarcinoma cells to hypoxia and reduces tumor growth by suppressing the cSrc/NF-kappaB survival pathway. PLoS ONE. 2009;4:e8059 pubmed publisher
    ..These findings underscore a role for GD3 in hypoxia susceptibility by disabling the c-Src/NF-kappaB survival pathway resulting in lower Mn-SOD expression, which may be of relevance in hepatocellular carcinoma therapy. ..
  42. Moon S, Kim H, Lee Y, Kim C. 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. J Biol Chem. 2004;279:33063-70 pubmed
    ..However, MMP-2 overexpression was not affected by cell proliferation. These findings suggest that the GD3 synthase gene represents a physiological modulator of VSMC responses that may contribute to plaque instability in atherosclerosis. ..
  43. Tempera I, Buchetti B, Lococo E, Gradini R, Mastronardi A, Mascellino M, et al. GD3 nuclear localization after apoptosis induction in HUT-78 cells. Biochem Biophys Res Commun. 2008;368:495-500 pubmed publisher
    ..This work advances the hypothesis that GD3 induces a post-translational modification of histone H1 thus influencing the apoptosis process through transcriptional activation/repression of specific genes. ..
  44. Zeng G, Gao L, Suetake K, Joshi R, Yu R. Variations in gene expression patterns correlated with phenotype of F-11 tumor cells whose expression of GD3-synthase is suppressed. Cancer Lett. 2002;178:91-8 pubmed
    ..Defining GD3-related genes may lead to identification of clinically relevant therapeutics and to understanding of the mechanism(s) by which ganglioside GD3 affects tumor growth and metastasis. ..
  45. Angata K, Suzuki M, McAuliffe J, Ding Y, Hindsgaul O, Fukuda M. Differential biosynthesis of polysialic acid on neural cell adhesion molecule (NCAM) and oligosaccharide acceptors by three distinct alpha 2,8-sialyltransferases, ST8Sia IV (PST), ST8Sia II (STX), and ST8Sia III. J Biol Chem. 2000;275:18594-601 pubmed