ライフサイエンスコーパス: ST6Gal I

1 beta-galactoside alpha2,6-sialyltransferase (ST6Gal-I).

2 beta-galactoside:alpha2-6-sialyltransferase (ST6Gal-I).

3 -galactosamide alpha-2,6-sialyltranferase I (ST6Gal-I).

4 tial for proper conformation and activity of ST6Gal I.

5 role of the S-sialylmotif of the same enzyme ST6Gal I.

6 lects for clonal variants with more abundant ST6Gal-I.

7 lylation of these integrins with recombinant ST6Gal-I.

8 olon epithelial cell line lacking endogenous ST6Gal-I.

9 and GnT-II or trans-Golgi enzymes GalT-I and ST6Gal-I.

10 and not on alpha2,6-sialic acids produced by ST6Gal-I.

11 ding is attenuated upon forced expression of ST6Gal-I.

12 ynthesized 13C-CMP-NeuAc to the desialylated ST6Gal-I.

13 ST6Gal I, a glycosyltransferase expressed by B cells, ca

14 at the coordinate up-regulation of gal-3 and ST6Gal-I, a feature that is characteristic of colon carc

15 Correspondingly, ST6Gal-I activity augments the expression of tumor-promo

16 Intriguingly, differences in ST6Gal-I activity do not affect the function of DR4 or D

17 heroid growth, and clonal variants with high ST6Gal-I activity preferentially survived in CSC culture

18 ated DNA damage, indicating that suppressing ST6Gal-I activity sensitizes inherently resistant cells

19 view summarizes the evidence suggesting that ST6Gal-I activity serves as an "off switch" for galectin

20 g TNFR1 at the cell surface via sialylation, ST6Gal-I acts as a functional switch to divert signaling

21 ST6Gal-I adds an alpha2,6-linked sialic acid to the term

22 The glycosyltransferase, ST6Gal-I, adds sialic acid in an alpha2-6 linkage to the

23 ST6Gal-I (alpha2,6-sialyltransferase) is expressed as tw

24 Sialylation of CD45 by the ST6Gal I also prevented galectin-1-induced clustering of

25 ST6Gal-I also augmented tumor-initiating potential.

26 ST6Gal-I also potentiates expression of the cell cycle r

27 ST6Gal-I also promoted resistance to gemcitabine and ena

28 precursor protein and the sialyltransferase ST6Gal I and is important in the pathogenesis of Alzheim

29 an nodes provided novel evidence for altered ST6Gal-I and GnT-IV glycotransferase activities in lung

30 cans and by other sialyltransferases such as ST6Gal-I and ST6GalNAc-I, forming alpha2,6-sialylated co

31 y 50% of colon adenocarcinomas) up-regulates ST6Gal-I and, in turn, increases sialylation of beta1 in

32 e in the expression of the sialyltransferase ST6Gal I, and an increase in the expression of the galac

33 lation, we forced constitutive expression of ST6Gal-I, and found that this strongly inhibited PMA-ind

34 Together, these findings place ST6Gal-I as a critical player in imparting gemcitabine r

35 These findings indicate a role for ST6Gal-I as a mediator of tumor progression, with its ex

36 Recipient mice that received ST6Gal I(-/-) B cells demonstrated reduced influenza-spe

37 that in many ways carries an imprint of the ST6Gal-I binding site.

38 rum deprivation, supporting the concept that ST6Gal-I confers a survival advantage.

39 yposialylation), through BACE1 inhibition or ST6Gal-I constitutive overexpression, eliminates VCAM-1

40 ialic acid residues were also observed, with ST6Gal-I deficiency causing loss on endothelium and ST3G

41 Diminished immune responses due to ST6Gal-I deficiency further correlate with constitutive

42 date the mechanisms involved, we report that ST6Gal-I deficiency induces immunoglobulin M (IgM) antig

43 ed the subcellular location and mechanism of ST6Gal I dimer formation, as well as the role of Cys res

44 ed increased dimer formation suggesting that ST6Gal I dimers may be critical in the oligomerization p

45 U937 cells with forced ST6Gal-I displayed TNFR1 with elevated alpha2-6 sialylat

46 Pulse-chase analysis demonstrated that the ST6Gal I disulfide-bonded dimer forms in the endoplasmic

47 Preventing ST6Gal-I down-regulation (and therefore integrin hyposia

48 Importantly, ST6Gal-I down-regulation results from cleavage by the BA

49 EK, but not phosphoinositide 3-kinase, block ST6Gal-I down-regulation, integrin hyposialylation, and

50 estingly, macrophage differentiation induces ST6Gal-I down-regulation, leading to reduced alpha2-6 si

51 inhibits galectin-1 death, we expressed the ST6Gal I enzyme in a galectin-1-sensitive murine T cell

52 SAalpha2,6Gal sequences, created by the ST6Gal I enzyme, are present on medullary thymocytes res

53 e for the first time the in vivo role of the ST6Gal-I enzyme in the growth and differentiation of spo

54 spondingly, at these later time points, high ST6Gal-I expressers displayed sustained activation of th

55 atient-derived xenograft tumors enriched for ST6Gal-I-expressing cells relative to pair-matched untre

56 ST6Gal I expression abrogated the reduction in CD45 tyro

57 ST6Gal I expression reduced galectin-1 binding to the ce

58 cells following viral infection, suggesting ST6Gal I expression remains high on activated B cells in

59 We demonstrate that the loss of ST6Gal I expression results in similar influenza infecti

60 Modulating ST6Gal-I expression in pancreatic and ovarian cancer cel

61 tive enrichment in clonal variants with high ST6Gal-I expression is observed upon prolonged serum dep

62 these results, serum-starved cells with high ST6Gal-I expression maintain a greater number of S phase

63 Similarly, ST6Gal-I expression was restricted to basal epidermal la

64 Blockade of ST6Gal-I expression with short interfering RNA reversed

65 PDAC cells, we found that knockdown (KD) of ST6Gal-I expression, as well as removal of surface alpha

66 tive enrichment of clonal variants with high ST6Gal-I expression, further substantiating a role for S

67 ls exhibited a corresponding upregulation of ST6Gal-I expression.

68 ST6Gal-I expressors (with alpha2-6 sialylated beta1 inte

69 Removal of alpha2-6 sialic acids from ST6Gal-I expressors by neuraminidase treatment restores

70 Finally, we show that beta1 integrins from ST6Gal-I expressors have increased association with tali

71 tal SW48 colonocytes (unsialylated), whereas ST6Gal-I expressors were protected.

72 er number of S phase cells compared with low ST6Gal-I expressors, reflecting enhanced proliferation.

73 However, mechanisms by which ST6Gal-I facilitates tumor progression remain poorly und

74 Galbeta1-4GlcNAc:alpha2-6-sialyltransferase (ST6Gal I); formerly ST6N).

75 sferase of protein Asn-linked glycosylation (ST6Gal I) forms disulfide-bonded dimers that exhibit dec

76 HO-K1 cells indicated that expression of the ST6Gal I gene causes selective 9-O-acetylation of alpha2

77 Thus, manipulating ST6Gal I gene expression may have therapeutic potential

78 D22 and ST6Gal-I knockout mice revealed that ST6Gal-I-generated B cell CD22L plays a role in splenic

79 c and BM-derived DCs, which does not contain ST6Gal-I-generated sialic acids and which, unlike the B

80 e oligomerization process involved in stable ST6Gal I Golgi localization.

81 sm is not the predominant mechanism used for ST6Gal I Golgi localization.

82 Although the recombinant soluble form of ST6Gal I has six cysteines, quantitative analysis indica

83 enon is reproducible by stable expression of ST6Gal I in parental CHO cells, but not upon transfectio

84 beta1-integrin function, we stably expressed ST6Gal-I in a colon epithelial cell line lacking endogen

85 xpression, further substantiating a role for ST6Gal-I in cell survival.

86 hairpin RNA (shRNA)-mediated attenuation of ST6Gal-I in colon carcinoma cells with elevated endogeno

87 hese results implicate a functional role for ST6Gal-I in fostering tumor cell survival within the ser

88 This first in vivo evidence for a role of ST6Gal-I in tumor progression was confirmed using a nove

89 ubset development, whereas the DC-associated ST6Gal-I-independent CD22L may be required for the maint

90 sfection of CHO-GD3-OAc(-) mutant cells with ST6Gal-I induced 9-O-acetylation specifically on sialyla

91 Finally, we found that ST6Gal-I induced expression of the key tumor-promoting t

92 The ST6Gal I is a sialyltransferase that functions in the la

93 The ST6Gal I is expressed as two isoforms with a single amin

94 c cells and primary human CD14(+) monocytes, ST6Gal-I is down-regulated, leading to beta1 hyposialyla

95 ST6Gal-I is itself a glycoprotein, and in this initial a

96 Here we show that ST6Gal-I is upregulated in ovarian and pancreatic carcin

97 The alpha-2,6-sialyltransferase (ST6Gal-I) is a key enzyme that regulates the distributio

98 the stable or transient localization of the ST6Gal I isoforms in the Golgi.

99 These two ST6Gal I isoforms were used to explore the role of the b

100 We have found that the ST6Gal-I isoforms are phosphorylated on luminal Ser and

101 ST6Gal-I KD also alters mRNA expression of key gemcitabi

102 ST6Gal-I KD in S2-013 cells increases gemcitabine-mediat

103 Using ST6Gal-I knockdown and forced overexpression colon carci

104 ing pancreatic and ovarian cancer cells with ST6Gal-I knockdown or overexpression, we determined that

105 ubcutaneous tumor formation was inhibited by ST6Gal-I knockdown, whereas in a chemically induced tumo

106 of splenic and BM B cell subsets in CD22 and ST6Gal-I knockout mice revealed that ST6Gal-I-generated

107 isoforms of the alpha2,6-sialyltransferase (ST6Gal I) leads to differences in their trafficking, pro

108 , we find that serum-starved cells with high ST6Gal-I levels exhibit increased activation of prosurvi

109 nded TNF treatment (6-24 h), cells with high ST6Gal-I levels exhibited resistance to TNF-induced apop

110 ine-resistant MiaPaCa-2 cells display higher ST6Gal-I levels than treatment-naive cells along with a

111 In normal colon, ST6Gal-I localized selectively to the base of crypts, wh

112 metastasis and poor survival, and therefore ST6Gal-I-mediated hypersialylation likely plays a role i

113 transfer purified B cells from wild-type or ST6Gal I(-/-) mice into B cell-deficient (microMT(-/-))

114 At later memory time points, ST6Gal I(-/-) mice show comparable numbers of IgG influe

115 ntiviral B cell immune response, we infected ST6Gal I(-/-) mice with influenza A/HKx31.

116 ST6Gal-I mRNA has been reported to be upregulated in hum

117 versed collagen binding back to the level of ST6Gal-I nonexpressors, confirming that alpha2-6 sialyla

118 Tissues of ST6Gal-I null mice showed minimal binding of an alpha2-6

119 Up-regulation of ST6Gal-I occurs in many cancers, including colon carcino

120 ith TRAIL, implicating a selective effect of ST6Gal-I on the Fas receptor.

121 g that O-acetylation is not induced when the ST6Gal I or ST8Sia I cDNAs are overexpressed in SV40 T a

122 umor initiation model, mice with conditional ST6Gal-I overexpression exhibited enhanced tumorigenesis

123 arian and pancreatic cancer cell models with ST6Gal-I overexpression or knockdown, we find that serum

124 This suggests that the bulk of the ST6Gal-I phosphorylation is occurring in the Golgi.

125 Elevated ST6Gal-I positively correlates with metastasis and poor

126 Additionally, KD of ST6Gal-I potentiates gemcitabine-induced DNA damage as m

127 Because the ST6Gal I preferentially utilizes N-glycans as acceptor s

128 Collectively, our results suggest that ST6Gal-I promotes tumorigenesis and may serve as a regul

129 Here, we show upregulated ST6Gal-I protein in several epithelial cancers, includin

130 s has limited immunochemical analysis of the ST6Gal-I protein.

131 , S2-LM7AA, and S2-013, exhibit up-regulated ST6Gal-I relative to parental Suit2 cells.

132 Protein glycosylation by ST6Gal-I restricts access of antigen receptors and Shp-1

133 BACE1 up-regulation, ST6Gal-I shedding, beta1 hyposialylation, and alpha4beta

134 th suppressed BCR signaling, B cells lacking ST6Gal I showed a net redistribution of the BCR to clath

135 her neuraminidase treatment or expression of ST6Gal-I shRNA markedly enhanced TNFalpha-mediated apopt

136 ged by exogenously administering recombinant ST6Gal I sialyltransferase and azide-modified CMP-Neu5Ac

137 duces a down-regulation in expression of the ST6Gal I sialyltransferase.

138 The ST6Gal-I sialyltransferase adds an alpha2-6-linked siali

139 Here, we report a novel role for the ST6Gal-I sialyltransferase in gemcitabine resistance.

140 The ST6Gal-I sialyltransferase produces Siglec ligands for t

141 onocyte/macrophage lineage down-regulate the ST6Gal-I sialyltransferase via a protein kinase C/Ras/ER

142 In this study, we report that the ST6Gal-I sialyltransferase, an enzyme up-regulated in nu

143 alylation of the TNFR1 death receptor by the ST6Gal-I sialyltransferase.

144 ds, a carbohydrate modification added by the ST6Gal-I sialyltransferase.

145 ion of the CD22 glycan ligand(s) produced by ST6Gal-I sialyltransferase.

146 a-galactoside alpha-2,6-sialyltransferase 1 (ST6Gal-I) sialyltransferase, which is up-regulated in nu

147 Although both ST3Gal-IV and ST6Gal-I sialyltransferases mask galactose linkages impl

148 Expression of the ST6Gal I specifically resulted in increased sialylation

149 entify the death receptor, Fas (CD95), as an ST6Gal-I substrate, and show that alpha2-6 sialylation o

150 B cells deficient in the enzyme (ST6Gal I) that forms the CD22 ligand show suppressed BCR

151 as-dependent alteration in the expression of ST6Gal I, the enzyme that adds alpha2-6-linked sialic ac

152 pha2-6 sialylation and increased activity of ST6Gal-I, the Golgi glycosyltransferase that creates alp

153 that that uses alpha-2,6-sialyltransferase (ST6Gal-I) to enzymatically add 13C-N-acetylneuraminic ac

154 Furthermore, the ST6Gal I transfectants produced no intracranial tumors i

155 Galbeta1,4GlcNAc alpha2,6-sialyltransferase (ST6Gal I) transfectants were made to replace the endogen

156 d vector-transfected control cells in vitro, ST6Gal I transfection abolished invasion in vitro and in

157 mice in comparison with animals deficient in ST6Gal-I (transfers alpha2-6-linked sialic acid to Galbe

158 FR1 sialylation, we generated overexpressing ST6Gal-I transgenic mice.

159 Notably, ST6Gal-I upregulation in cancer cells conferred hallmark

160 r previous study the larger L-sialylmotif of ST6Gal I was analyzed by site-directed mutagenesis, whic

161 The catalytic domain from rat ST6Gal-I was expressed in mammalian HEK293 cells.

162 ST6Gal-I was highly expressed in induced pluripotent ste

163 sion due to the various 13C-NeuAc adducts on ST6Gal-I was observed in a 3D experiment correlating 1H-

164 uced by the human alpha2-6 sialyltransferase ST6Gal-I, were identified as potent anti-inflammatory me

165 The glycosyltransferase ST6Gal-I, which adds alpha2-6-linked sialic acids to sub

166 ialyltransferases ST3Gal-III, ST3Gal-IV, and ST6Gal-I, which together are responsible for addition of

167 s, we investigated further an association of ST6Gal-I with cancer stem cells (CSC).

168 ed removal of the native NeuAc residues from ST6Gal-I with neuraminidase, separation of the neuramind