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sialyltransferase

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https://www.readbyqxmd.com/read/29057592/the-role-of-sialic-acids-in-the-immune-recognition-of-xenografts
#1
REVIEW
Beth M French, Selin Sendil, Richard N Pierson, Agnes M Azimzadeh
Presentation of sialic acid (Sia) varies among different tissues and organs within each species, and between species. This diversity has biologically important consequences regarding the recognition of cells by "xeno" antibodies (Neu5Gc vs Neu5Ac). Sia also plays a central role in inflammation by influencing binding of the asialoglycoprotein receptor 1 (ASGR-1), Siglec-1 (Sialoadhesin), and cellular interactions mediated by the selectin, integrin, and galectin receptor families. This review will focus on what is known about basic Sia structure and function in association with xenotransplantation, how changes in sialylation may occur in this context (through desialylation or changes in sialyltransferases), and how this fundamental pathway modulates adhesive and cell activation pathways that appear to be particularly crucial to homeostasis and inflammation for xenografts...
October 22, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29030743/mir-182-and-mir-135b-mediate-the-tumorigenesis-and-invasiveness-of-colorectal-cancer-cells-via-targeting-st6galnac2-and-pi3k-akt-pathway
#2
Li Jia, Shihua Luo, Xiang Ren, Yang Li, Jialei Hu, Bing Liu, Lifen Zhao, Yujia Shan, Huimin Zhou
BACKGROUND: Metastasis is a leading cause of cancer-related death including colorectal cancer (CRC). MicroRNAs are known to regulate cancer pathways and to be expressed aberrantly in cancer. Aberrant sialylation is closely associated with malignant phenotype of tumor cells, including invasiveness and metastasis. AIM: This study aimed to investigate the association of miR-182 and miR-135b with proliferation and invasion by targeting sialyltransferase ST6GALNAC2 in CRC cells and explore the potential molecular mechanism...
October 13, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28935102/biosynthesis-of-legionaminic-acid-and-its-incorporation-into-glycoconjugates
#3
Ian C Schoenhofen, N Martin Young, Michel Gilbert
Legionaminic acids are analogs of sialic acid that occur in cell surface glycoconjugates of several bacteria. Because legionaminic acids share the same stereochemistry as sialic acid but differ at C7 and C9, they are interesting analogs to probe the impact of varying exocyclic moieties (C7-C9) on biological activities such as susceptibilities to sialidases, interactions with Siglecs and immunogenicity. There are currently no reports on the bacterial enzymes that transfer legionaminic acids to these cell surface glycoconjugates, but some mammalian and bacterial sialyltransferases display donor promiscuity and can use CMP-Leg5,7Ac2 efficiently enough to transfer Leg5,7Ac2 to their natural acceptor glycans...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28926673/combinatorial-genome-and-protein-engineering-yields-monoclonal-antibodies-with-hypergalactosylation-from-cho-cells
#4
Cheng-Yu Chung, Qiong Wang, Shuang Yang, Sean A Ponce, Brian J Kirsch, Hui Zhang, Michael J Betenbaugh
One of the key quality attributes of monoclonal antibodies is the glycan pattern and distribution. Two terminal galactose residues typically represent a small fraction of the total glycans from antibodies. However, antibodies with defined glycosylation properties including enhanced galactosylation have been shown to exhibit altered properties for these important biomedical modalities. In this study, the disruption of two α-2,3 sialyltransferases (ST3GAL4 and ST3GAL6) from Chinese Hamster Ovary (CHO) cells was combined with protein engineering of the Fc region to generate an IgG containing 80% bigalactosylated and fucosylated (G2F) glycoforms...
July 7, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28925387/a-vital-sugar-code-for-ricin-toxicity
#5
Jasmin Taubenschmid, Johannes Stadlmann, Markus Jost, Tove Irene Klokk, Cory D Rillahan, Andreas Leibbrandt, Karl Mechtler, James C Paulson, Julian Jude, Johannes Zuber, Kirsten Sandvig, Ulrich Elling, Thorsten Marquardt, Christian Thiel, Christian Koerner, Josef M Penninger
Ricin is one of the most feared bioweapons in the world due to its extreme toxicity and easy access. Since no antidote exists, it is of paramount importance to identify the pathways underlying ricin toxicity. Here, we demonstrate that the Golgi GDP-fucose transporter Slc35c1 and fucosyltransferase Fut9 are key regulators of ricin toxicity. Genetic and pharmacological inhibition of fucosylation renders diverse cell types resistant to ricin via deregulated intracellular trafficking. Importantly, cells from a patient with SLC35C1 deficiency are also resistant to ricin...
September 19, 2017: Cell Research
https://www.readbyqxmd.com/read/28903359/expression-of-sialyl-tn-sugar-antigen-in-bladder-cancer-cells-affects-response-to-bacillus-calmette-gu%C3%A3-rin-bcg-and-to-oxidative-damage
#6
Paulo F Severino, Mariana Silva, Mylene Carrascal, Nadia Malagolini, Mariella Chiricolo, Giulia Venturi, Annalisa Astolfi, Mariangela Catera, Paula A Videira, Fabio Dall'Olio
The sialyl-Tn (sTn) antigen is an O-linked carbohydrate chain aberrantly expressed in bladder cancer (BC), whose biosynthesis is mainly controlled by the sialyltransferase ST6GALNAC1. Treatment with Bacillus Calmette-Guérin (BCG) is the most effective adjuvant immunotherapy for superficial BC but one third of the patients fail to respond. A poorly understood correlation between the expression of sTn and BC patient's response to BCG was previously observed. By analyzing tumor tissues, we showed that patients with high ST6GALNAC1 and IL-6 mRNA expression were BCG responders...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28898525/analyses-of-n-linked-glycans-of-prp-s-c-revealed-predominantly-2-6-linked-sialic-acid-residues
#7
Elizaveta Katorcha, Ilia V Baskakov
Mammalian prions (PrP(S)(c) ) consist of misfolded, conformationally altered, self-replicating states of the sialoglycoprotein called prion protein or PrP(C) . Recent studies revealed that the sialylation status of PrP(S)(c) plays a major role in evading innate immunity and infecting a host. Establishing the type of linkage by which sialic acid residues are attached to galactose is important, as it helps to identify the sialyltransferases responsible for sialylating PrP(C) and outline strategies for manipulating the sialyation status of PrP(S)(c) ...
September 12, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28783175/contribution-of-vascular-endothelial-growth-factor-receptor-2-sialylation-to-the-process-of-angiogenesis
#8
P Chiodelli, S Rezzola, C Urbinati, F Federici Signori, E Monti, R Ronca, M Presta, M Rusnati
Vascular endothelial growth factor receptor-2 (VEGFR2) is the main pro-angiogenic receptor expressed by endothelial cells (ECs). Using surface plasmon resonance, immunoprecipitation, enzymatic digestion, immunofluorescence and cross-linking experiments with specific sugar-binding lectins, we demonstrated that VEGFR2 bears both α,1-fucose and α(2,6)-linked sialic acid (NeuAc). However, only the latter is required for VEGF binding to VEGFR2 and consequent VEGF-dependent VEGFR2 activation and motogenic response in ECs...
August 7, 2017: Oncogene
https://www.readbyqxmd.com/read/28764968/production-of-human-milk-oligosaccharides-by-enzymatic-and-whole-cell-microbial-biotransformations
#9
Georg A Sprenger, Florian Baumgärtner, Christoph Albermann
Human milk oligosaccharides (HMO) are almost unique constituents of breast milk and are not found in appreciable amounts in cow milk. Due to several positive aspects of HMO for the development, health, and wellbeing of infants, production of HMO would be desirable. As a result, scientists from different disciplines have developed methods for the preparation of single HMO compounds. Here, we review approaches to HMO preparation by (chemo-)enzymatic syntheses or by whole-cell biotransformation with recombinant bacterial cells...
July 29, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28717006/extrinsic-sialylation-is-dynamically-regulated-by-systemic-triggers-in-vivo
#10
COMPARATIVE STUDY
Charles T Manhardt, Patrick R Punch, Christopher W L Dougher, Joseph T Y Lau
Recent reports have documented that extracellular sialyltransferases can remodel both cell-surface and secreted glycans by a process other than the canonical cell-autonomous glycosylation that occurs within the intracellular secretory apparatus. Despite association of the abundance of these extracellular sialyltransferases, particularly ST6Gal-1, with disease states such as cancer and a variety of inflammatory conditions, the prevalence of this extrinsic glycosylation pathway in vivo remains unknown. Here we observed no significant extrinsic sialylation in resting mice, suggesting that extrinsic sialylation is not a constitutive process...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28687873/%C3%AE-2-6-linked-sialic-acid-serves-as-a-high-affinity-receptor-for-cancer-oncolytic-virotherapy-with-newcastle-disease-virus
#11
Qian Li, Ding Wei, Fei Feng, Xi-Long Wang, Can Li, Zhi-Nan Chen, Huijie Bian
PURPOSE: Newcastle disease virus (NDV) has been applied to oncolytic virotherapy for decades due to its naturally oncolytic property. In spite of the substantiation of the sialic acid receptors of NDV on host cells, knowledge of preference of sialic acid linkage in viral attachment and oncolytic effect is lacking and imperative to be elucidated. METHODS: Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues were used to determine the affinity and the preference of sialic acid receptor...
November 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28681122/lewis-x-antigen-is-associated-to-head-and-neck-squamous-cell-carcinoma-survival
#12
Martín E Rabassa, Adrian Pereyra, Liliana Pereyra, Amada Segal-Eiras, Martín C Abba, Maria V Croce
Head and neck squamous cell carcinoma (HNSCC) is an aggressive disease with poor prognosis without appropriate prognostic markers. Previous research shows that Lewis antigens have been involved in carcinoma dissemination and patients´ survival. Fucosyl and sialyltransferases are the enzymes implicated in the Lewis antigens synthesis. The purpose of this study was to evaluate the prognostic utility of Lewis antigens in HNSCC. We conducted a prospective research including histological samples from 79 patients with primary HNSCC...
July 5, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28553930/%C3%AE-2-6-sialylation-mediates-hepatocellular-carcinoma-growth-in-vitro-and-in-vivo-by-targeting-the-wnt-%C3%AE-catenin-pathway
#13
Y Zhao, A Wei, H Zhang, X Chen, L Wang, H Zhang, X Yu, Q Yuan, J Zhang, S Wang
Abnormal sialylation due to overexpression of sialyltransferases has been associated with tumorigenesis and tumor progression. Although ST6Gal-I influences cancer persistence and progression by affecting various receptors, the underlying mechanisms and mediators remain largely obscure, especially in hepatocellular carcinoma (HCC). We found that ST6Gal-I expression was markedly upregulated in HCC tissues and cells, high levels being associated with aggressive phenotype and poor prognosis. Furthermore, we examined the roles and mechanisms of ST6Gal-I in HCC tumorigenesis and metastasis in vitro and in vivo...
May 29, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28550122/the-blood-borne-sialyltransferase-st6gal-1-is-a-negative-systemic-regulator-of-granulopoiesis
#14
Christopher W L Dougher, Alexander Buffone, Michael J Nemeth, Mehrab Nasirikenari, Eric E Irons, Paul N Bogner, Joseph T Y Lau
Responding to systemic demands in producing and replenishing end-effector blood cells is predicated on the appropriate delivery and interpretation of extrinsic signals to the HSPCs. The data presented herein implicate the systemic, extracellular form of the glycosyltransferase ST6Gal-1 in the regulation of late-stage neutrophil development. ST6Gal-1 is typically a membrane-bound enzyme sequestered within the intracellular secretory apparatus, but an extracellular form is released into the blood from the liver...
August 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28537895/interaction-of-glycosphingolipids-gd3-and-gd2-with-growth-factor-receptors-maintains-breast-cancer-stem-cell-phenotype
#15
Yuh-Jin Liang, Chen-Yu Wang, I-An Wang, Yi-Wen Chen, Li-Tzu Li, Chuang-Yu Lin, Ming-Yi Ho, Tsung-Lung Chou, Ya-Hui Wang, Shih-Pin Chiou, Yu-Ju Lin, John Yu
Many studies have suggested that disialogangliosides, GD2 and GD3, are involved in the development of various tumor types. However, the functional relationships between ganglioside expression and cancer development or aggressiveness are not fully described. GD3 is upregulated 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 correlate with reduced overall patient survival...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28512058/downregulation-of-mir-224-and-let-7i-contribute-to-cell-survival-and-chemoresistance-in-chronic-myeloid-leukemia-cells-by-regulating-st3gal-iv-expression
#16
Huimin Zhou, Yang Li, Bing Liu, Yujia Shan, Yan Li, Lifen Zhao, Zhen Su, Li Jia
Acquired resistance to imatinib is frequently associated with poor clinical outcome of chronic myeloid leukemia (CML) patient. To date, evidence indicates that protein glycosylation and its upstream regulators might be implicated in tumorigenesis and chemoresistance occurrence. In current study we initially explored N-glycan profiles on the surface of CML cell lines and bone marrow mononuclear cells (BMMC) of CML patients by using mass spectrometry (MS) analysis. An elevated sialylation was detected in K562R cells (CML cells with imatinib resistance phenotype) compare to K562 cells...
August 30, 2017: Gene
https://www.readbyqxmd.com/read/28500031/labeling-glycans-on-living-cells-by-a-chemoenzymatic-glycoengineering-approach
#17
Ruben T Almaraz, Yanhong Li
Structural glycobiology has traditionally been a challenging field due to a limited set of tools available to investigate the diverse and complex glycan molecules. However, we cannot ignore that glycans play critical roles in health as well as in disease, and are present in more than 50% of all proteins and on over 80% of all surface proteins. Chemoenzymatic glycoengineering (CGE) methods are a powerful set of tools to synthesize complex glycans, but the full potential of these methods have not been explored in cell biology yet...
June 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28474804/active-site-his85-of-pasteurella-dagmatis-sialyltransferase-facilitates-productive-sialyl-transfer-and-so-prevents-futile-hydrolysis-of-cmp-neu5ac
#18
Katharina Schmölzer, Manuel Eibinger, Bernd Nidetzky
Sialyltransferases of the GT-80 glycosyltransferase family are considered multifunctional because of the array of activities detected. They exhibit glycosyl transfer, trans-sialylation, and hydrolysis activities. How these enzymes utilize their active-site residues in balancing the different enzymatic activities is not well understood. In this study of Pasteurella dagmatis α2,3sialyltransferase, we show that the conserved His85 controls efficiency and selectivity of the sialyl transfer. A His85→Asn variant was 200 times less efficient than wild-type for sialylation of lactose, and exhibited relaxed site selectivity to form not only the α2,3- but also the α2,6-sialylated product (21 %)...
May 5, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28467974/expression-of-sialyl-tn-sugar-antigen-in-bladder-cancer-cells-affects-response-to-bacillus-calmette-gu%C3%A3-rin-bcg-and-to-oxidative-damage
#19
Paulo F Severino, Mariana Silva, Mylene Carrascal, Nadia Malagolini, Mariella Chiricolo, Giulia Venturi, Annalisa Astolfi, Mariangela Catera, Paula A Videira, Fabio Dall'Olio
The sialyl-Tn (sTn) antigen is an O-linked carbohydrate chain aberrantly expressed in bladder cancer (BC), whose biosynthesis is mainly controlled by the sialyltransferase ST6GALNAC1. Treatment with Bacillus Calmette-Guérin (BCG) is the most effective adjuvant immunotherapy for superficial BC but one third of the patients fail to respond. A poorly understood correlation between the expression of sTn and BC patient's response to BCG was previously observed. By analyzing tumor tissues, we showed that patients with high ST6GALNAC1 and IL-6 mRNA expression were BCG responders...
April 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28465212/cell-culture-media-supplemented-with-raffinose-reproducibly-enhances-high-mannose-glycan-formation
#20
David Brühlmann, Anais Muhr, Rebecca Parker, Thomas Vuillemin, Blanka Bucsella, Franka Kalman, Serena Torre, Fabio La Neve, Antonio Lembo, Tobias Haas, Markus Sauer, Jonathan Souquet, Hervé Broly, Jürgen Hemberger, Martin Jordan
Glycosylation plays a pivotal role in pharmacokinetics and protein physiochemical characteristics. In particular, effector functions including antibody-dependent cell-mediated cytotoxicity (ADCC) can be desired, and it has been described that high-mannose species exhibited enhanced ADCC. In this work we present the trisaccharide raffinose as a novel cell culture medium supplement to promote high mannose N-glycans in fed-batch cultures, which is sought after in the development of biosimilars to match the quality profile of the reference medicinal product (RMP) also...
April 29, 2017: Journal of Biotechnology
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