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sialyltransferase

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https://www.readbyqxmd.com/read/28218742/mirna-expression-profiles-reveal-the-involvement-of-mir-26a-mir-548l-and-mir-34a-in-hepatocellular-carcinoma-progression-through-regulation-of-st3gal5
#1
Hongjiao Cai, Huimin Zhou, Yuan Miao, Nana Li, Lifen Zhao, Li Jia
MicroRNAs (miRNAs) have key roles in comprehensive physiological and pathological processes by targeting specific genes through translational repression. Identification of miRNAs related to metastasis enables us to obtain better insight into cancer development. In the current study, we investigated the miRNA expressional profiles in the highly invasive human hepatocellular carcinoma cell line MHCC97-H and MHCC97-L with lower metastatic potential using miRNA microarrays. By quantitative real-time PCR, we confirmed the results of miRNA experiments...
February 20, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28182562/in-silico-modeling-of-the-functional-role-of-reduced-sialylation-in-sodium-and-potassium-channel-gating-of-mouse-ventricular-myocytes
#2
Dongping Du, Hui Yang, Andrew R Ednie, Eric S Bennett
Cardiac ion channels are highly glycosylated membrane proteins, with up to 30% of the protein's mass containing glycans. Heart diseases often accompany individuals with congenital disorders of glycosylation (CDG). However, cardiac dysfunction among CDG patients is not yet fully understood. There is an urgent need to study how aberrant glycosylation impacts cardiac electrical signaling. Our previous works reported that congenitally reduced sialylation achieved through deletion of the sialyltransferase gene, ST3Gal4, leads to altered gating of voltage-gated Na+ and K+ channels (Nav and Kv, respectively)...
February 6, 2017: IEEE Journal of Biomedical and Health Informatics
https://www.readbyqxmd.com/read/28165727/transition-state-based-sialyltransferase-inhibitors-mimicking-oxocarbenium-ion-by-simple-amide
#3
Jian Guo, Wenming Li, Weiwei Xue, Xin-Shan Ye
In the new transition-state-based sialyltransferase inhibitors, an amide group was placed at the corresponding C-2 position of CMP-sialic acid to mimic the geometry and charge distribution in the transition-state, and simple aromatic or aliphatic rings were used instead of sialic acid moiety. All synthetic compounds exhibited excellent α(2-6)-sialyltransferase inhibition, resulting in up to a 2600-fold higher affinity for the enzyme than CMP-Neu5Ac, suggesting that amide is a key element for simulating transition-state features...
February 6, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28154177/glycosyltransferase-st6gal-i-protects-tumor-cells-against-serum-growth-factor-withdrawal-by-enhancing-survival-signaling-and-proliferative-potential
#4
Colleen M Britain, Kaitlyn A Dorsett, Susan L Bellis
A hallmark of cancer cells is the ability to survive and proliferate when challenged with stressors such as growth factor insufficiency. In the current study we report a novel glycosylation-dependent mechanism that protects tumor cells from serum growth factor withdrawal. Results herein suggest that the ST6Gal-I sialyltransferase, which is upregulated in numerous cancers, promotes the survival of serum-starved cells. Using ovarian and pancreatic cancer cell models with ST6Gal-I overexpression or knockdown, we find that serum-starved cells with high ST6Gal-I levels exhibit increased activation of pro-survival signaling molecules including pAkt, p-p70S6K and pNFkB...
January 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28138383/systematic-chemoenzymatic-synthesis-of-o-sulfated-sialyl-lewis-x-antigens
#5
Abhishek Santra, Hai Yu, Nova Tasnima, Musleh M Muthana, Yanhong Li, Jie Zeng, Nicholas J Kenyond, Angelique Y Louie, Xi Chen
O-Sulfated sialyl Lewis x antigens play important roles in nature. However, due to their structural complexity, they are not readily accessible by either chemical or enzymatic synthetic processes. Taking advantage of a bacterial sialyltransferase mutant that can catalyze the transfer of different sialic acid forms from the corresponding sugar nucleotide donors to Lewis x antigens which are fucosylated glycans as well as an efficient one-pot multienzyme (OPME) sialylation system, O-sulfated sialyl Lewis x antigens containing different sialic acid forms and O-sulfation at different locations were systematically synthesized by chemoenzymatic methods...
April 1, 2016: Chemical Science
https://www.readbyqxmd.com/read/28134951/converting-pasteurella-multocida-%C3%AE-2-3-sialyltransferase-1-pmst1-to-a-regioselective-%C3%AE-2-6-sialyltransferase-by-saturation-mutagenesis-and-regioselective-screening
#6
John B McArthur, Hai Yu, Jie Zeng, Xi Chen
A microtiter plate-based screening assay capable of determining the activity and regioselectivity of sialyltransferases was developed. This assay was used to screen two single-site saturation libraries of Pasteurella multocida α2-3-sialyltransferase 1 (PmST1) for α2-6-sialyltransferase activity and total sialyltransferase activity. PmST1 double mutant P34H/M144L was found to be the most effective α2-6-sialyltransferase and displayed 50% reduced donor hydrolysis and 50-fold reduced sialidase activity compared to the wild-type PmST1...
January 30, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28035776/direct-enzymatic-branch-end-extension-of-glycocluster-presented-glycans-an-effective-strategy-for-programming-glycan-bioactivity
#7
Carlos Bayón, Ning He, Mario Deir-Kaspar, Pilar Blasco, Sabine André, Hans-Joachim Gabius, Ángel Rumbero, Jesús Jiménez-Barbero, Wolf-Dieter Fessner, María J Hernáiz
The sequence of a glycan and its topology of presentation team up to determine the specificity and selectivity of recognition by saccharide receptors (lectins). Structure-activity analysis would be furthered if the glycan part of a glycocluster could be efficiently elaborated in situ while keeping all other parameters constant. By using a bacterial α2,6-sialyltransferase and a small library of bi- to tetravalent glycoclusters, we illustrate the complete conversion of scaffold-presented lactoside units into two different sialylated ligands based on N-acetyl/glycolyl-neuraminic acid incorporation...
January 31, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28032858/functional-roles-of-sialylation-in-breast-cancer-progression-through-mir-26a-26b-targeting-st8sia4
#8
Xiaolu Ma, Weijie Dong, Zhen Su, Lifen Zhao, Yuan Miao, Nana Li, Huimin Zhou, Li Jia
Sialylation is one of the altered glycosylation patterns associated with cancer progression. In this study, we investigated the N-glycan profiles of breast cancer patients and cell lines to reveal sialylation associated with breast cancer progression, and provided new evidences of miRNA-mediated sialylation. MALDI-TOF MS analysis revealed that N-glycans found in breast cancer tissues and breast cancer cell MDA-MB-231 featured increased levels of sialylation compared with adjacent tissues and normal breast epithelial cell MCF-10A...
December 29, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/28032597/elevation-of-%C3%AE-galactoside-%C3%AE-2-6-sialyltransferase-1-in-a-fructoseresponsive-manner-promotes-pancreatic-cancer-metastasis
#9
Chi-Che Hsieh, Yi-Ming Shyr, Wen-Ying Liao, Tien-Hua Chen, Shin-E Wang, Peir-Chuen Lu, Pei-Yu Lin, Yan-Bo Chen, Wan-Yu Mao, Hsin-Ying Han, Michael Hsiao, Wen-Bin Yang, Wen-Shan Li, Yuh-Pyng Sher, Chia-Ning Shen
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive type of pancreatic cancer with clinical characteristics of local invasion and early metastasis. Recent cohort studies indicate high fructose intake is associated with an increase in pancreatic cancer risk. However, the mechanisms by which fructose promotes pancreatic tumorigenesis remain unclear. Herein, Kras+/LSLG12D mice were crossed with Elas-CreER transgenic mice to determine whether fructose intake directly contributes to tumor formation. Orthotopic tumor-xenograft experiments were performed to determine whether fructose substitution enhances the metastatic potential of PDAC cells...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28031460/the-inhibitory-role-of-%C3%AE-2-6-sialylation-in-adipogenesis
#10
Tomoko Kaburagi, Yasuhiko Kizuka, Shinobu Kitazume, Naoyuki Taniguchi
Adipose tissue plays critical roles in obesity and related diseases such as diabetes and cardiovascular diseases. Previous reports suggest that glycans, the most common posttranslational modifications, are involved in obesity-related diseases, but what type of glycan regulates adipogenesis during obesity remains unclear. In this study, we first quantified the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice...
February 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28002448/unique-molecular-patterns-uncovered-in-kawasaki-disease-patients-with-elevated-serum-gamma-glutamyl-transferase-levels-implications-for-intravenous-immunoglobulin-responsiveness
#11
Yue Wang, Zhen Li, Guang Hu, Shiying Hao, Xiaohong Deng, Min Huang, Miao Ren, Xiyuan Jiang, John T Kanegaye, Kee-Soo Ha, JungHwa Lee, Xiaofeng Li, Xuejun Jiang, Yunxian Yu, Adriana H Tremoulet, Jane C Burns, John C Whitin, Andrew Y Shin, Karl G Sylvester, Doff B McElhinney, Harvey J Cohen, Xuefeng B Ling
BACKGROUND: Resistance to intravenous immunoglobulin (IVIG) occurs in 10-20% of patients with Kawasaki disease (KD). The risk of resistance is about two-fold higher in patients with elevated gamma glutamyl transferase (GGT) levels. We sought to understand the biological mechanisms underlying IVIG resistance in patients with elevated GGT levels. METHOD: We explored the association between elevated GGT levels and IVIG-resistance with a cohort of 686 KD patients (Cohort I)...
2016: PloS One
https://www.readbyqxmd.com/read/27986075/knockdown-of-st6gal-i-increases-cisplatin-sensitivity-in-cervical-cancer-cells
#12
Xiaopeng Zhang, Chunchen Pan, Lei Zhou, Zhaogen Cai, Shufang Zhao, Donghong Yu
BACKGROUND: Sialyltransferase I (ST6Gal-I) is an enzyme involved in tumor metastasis that processes sialic acid precursors into their mature form, enabling them to regulate gene expression. However, the effect of ST6Gal-I on the biological behavior of cancer cells remain unclear. This study was the first to demonstrate the influence of ST6Gal-I on cisplatin sensitivity in cervical cancer cells. METHODS: Knockdown of ST6Gal-I was performed by shRNA and HeLa cells combination with cisplatin were tested...
December 16, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27975143/sialylation-of-n-glycans-mechanism-cellular-compartmentalization-and-function
#13
REVIEW
Gaurang P Bhide, Karen J Colley
Sialylated N-glycans play essential roles in the immune system, pathogen recognition and cancer. This review approaches the sialylation of N-glycans from three perspectives. The first section focuses on the sialyltransferases that add sialic acid to N-glycans. Included in the discussion is a description of these enzymes' glycan acceptors, conserved domain organization and sequences, molecular structure and catalytic mechanism. In addition, we discuss the protein interactions underlying the polysialylation of a select group of adhesion and signaling molecules...
February 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/27943633/integrated-genome-and-protein-editing-swaps-%C3%AE-2-6-sialylation-for-%C3%AE-2-3-sialic-acid-on-recombinant-antibodies-from-cho
#14
Cheng-Yu Chung, Qiong Wang, Shuang Yang, Bojiao Yin, Hui Zhang, Michael Betenbaugh
Immunoglobin G with α-2,6 sialylation has been reported to have an impact on antibody-dependent cellular cytotoxicity and anti-inflammatory efficacy. However, production of antibodies with α-2,6 sialylation from Chinese hamster ovary cells is challenging due to the inaccessibility of sialyltransferases for the heavy chain N-glycan site and the presence of exclusively α-2,3 sialyltransferases. In this study, combining mutations on the Fc regions to allow sialyltransferase accessibility with overexpression of α-2,6 sialyltransferase produced IgG with significant levels of both α-2,6 and α-2,3 sialylation...
December 12, 2016: Biotechnology Journal
https://www.readbyqxmd.com/read/27871859/alpha2-3-sialyltransferase-iii-knockdown-sensitized-ovarian-cancer-cells-to-cisplatin-induced-apoptosis
#15
Xiaoyu Wang, Yiting Zhang, Haiyingjie Lin, Yan Liu, Yi Tan, Jie Lin, Fenze Gao, Shaoqiang Lin
Emerging evidence indicates that β-galactoside-α2,3-sialyltransferase III (ST3Gal3) involves in development, inflammation, neoplastic transformation, and metastasis. However, the role of ST3Gal3 in regulating cancer chemoresistance remains elusive. Herein, we investigated the functional effects of ST3Gal3 in cisplatin-resistant ovarian cancer cells. We found that the levels of ST3Gal3 mRNA differed significantly among ovarian cancer cell lines. HO8910PM cells that have high invasive and metastatic capacity express elevated ST3Gal3 mRNA and are resistant to cisplatin, comparing to SKOV3 cells that have a lower level of ST3Gal3 expression and are more chemosensitive to cisplatin...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27835877/o-glycan-sialylation-alters-galectin-3-subcellular-localization-and-decreases-chemotherapy-sensitivity-in-gastric-cancer
#16
Sofia N Santos, Mara S Junqueira, Guilherme Francisco, Manuel Vilanova, Ana Magalhães, Marcelo Dias Baruffi, Roger Chammas, Adrian L Harris, Celso A Reis, Emerson S Bernardes
ST6GalNAc-I, the sialyltransferase responsible for sialyl-Tn (sTn) synthesis, has been previously reported to be positively associated with cancer aggressiveness. Here we describe a novel sTn-dependent mechanism for chemotherapeutic resistance. We show that sTn protects cancer cells against chemotherapeutic-induced cell death by decreasing the interaction of cell surface glycan receptors with galectin-3 and increasing its intracellular accumulation. Moreover, exogenously added galectin-3 potentiated the chemotherapeutics-induced cytotoxicity in sTn non-expressing cells, while sTn overexpressing cells were protected...
November 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27821620/tnf-up-regulates-st3gal4-and-sialyl-lewisx-expression-in-lung-epithelial-cells-through-an-intronic-atf2-responsive-element
#17
Florent Colomb, Marie-Ange Krzewinski-Recchi, Agata Steenackers, Audrey Vincent, Anne Harduin-Lepers, Philippe Delannoy, Sophie Groux-Degroote
We have previously shown that tumor necrosis factor (TNF) induced the up-regulation of the sialyltransferase gene ST3GAL4 (α2,3-sialyltransferase gene) BX transcript through mitogen- and stress-activated kinase 1/2 (MSK1/2), extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) signaling pathways. This up-regulation resulted in sialyl-Lewis(x) (sLe(x)) overexpression on high-molecular-weight glycoproteins in inflamed airway epithelium and increased the adhesion of Pseudomonas aeruginosa PAO1 and PAK strains to lung epithelial cells...
January 1, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/27820809/regulation-of-autoantibody-activity-by-the-il-23-th17-axis-determines-the-onset-of-autoimmune-disease
#18
René Pfeifle, Tobias Rothe, Natacha Ipseiz, Hans U Scherer, Stephan Culemann, Ulrike Harre, Jochen A Ackermann, Martina Seefried, Arnd Kleyer, Stefan Uderhardt, Benjamin Haugg, Axel J Hueber, Patrick Daum, Gordon F Heidkamp, Changrong Ge, Sybille Böhm, Anja Lux, Wolfgang Schuh, Iryna Magorivska, Kutty S Nandakumar, Erik Lönnblom, Christoph Becker, Diana Dudziak, Manfred Wuhrer, Yoann Rombouts, Carolien A Koeleman, René Toes, Thomas H Winkler, Rikard Holmdahl, Martin Herrmann, Stephan Blüml, Falk Nimmerjahn, Georg Schett, Gerhard Krönke
The checkpoints and mechanisms that contribute to autoantibody-driven disease are as yet incompletely understood. Here we identified the axis of interleukin 23 (IL-23) and the TH17 subset of helper T cells as a decisive factor that controlled the intrinsic inflammatory activity of autoantibodies and triggered the clinical onset of autoimmune arthritis. By instructing B cells in an IL-22- and IL-21-dependent manner, TH17 cells regulated the expression of β-galactoside α2,6-sialyltransferase 1 in newly differentiating antibody-producing cells and determined the glycosylation profile and activity of immunoglobulin G (IgG) produced by the plasma cells that subsequently emerged...
January 2017: Nature Immunology
https://www.readbyqxmd.com/read/27807044/golgi-enzymes-do-not-cycle-through-the-endoplasmic-reticulum-during-protein-secretion-or-mitosis
#19
Julien Villeneuve, Juan Duran, Margherita Scarpa, Laia Bassaganyas, Josse Van Galen, Vivek Malhotra
Golgi-specific sialyltransferase (ST) expressed as a chimera with the rapamycin-binding domain of mTOR, FRB, relocates to the endoplasmic reticulum (ER) in cells exposed to rapamycin that also express invariant chain (Ii)-FKBP in the ER. This result has been taken to indicate that Golgi-resident enzymes cycle to the ER constitutively. We show that ST-FRB is trapped in the ER even without Ii-FKBP upon rapamycin addition. This is because ER-Golgi-cycling FKBP proteins contain a C-terminal KDEL-like sequence, bind ST-FRB in the Golgi, and are transported together back to the ER by KDEL receptor-mediated retrograde transport...
January 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27798070/circulating-blood-and-platelets-supply-glycosyltransferases-that-enable-extrinsic-extracellular-glycosylation
#20
Melissa M Lee-Sundlov, David J Ashline, Andrew J Hanneman, Renata Grozovsky, Vernon N Reinhold, Karin M Hoffmeister, Joseph Ty Lau
Glycosyltransferases, usually residing within the intracellular secretory apparatus, also circulate in the blood. Many of these blood-borne glycosyltransferases are associated with pathological states, including malignancies and inflammatory conditions. Despite the potential for dynamic modifications of glycans on distal cell surfaces and in the extracellular milieu, the glycan-modifying activities present in systemic circulation have not been systematically examined. Here, we describe an evaluation of blood-borne sialyl-, galactosyl- and fucosyltransferase activities that act upon the four common terminal glycan precursor motifs, GlcNAc monomer, Gal(β3)GlcNAc, Gal(β4)GlcNAc and Gal(β3)GalNAc, to produce more complex glycan structures...
January 2017: Glycobiology
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