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https://www.readbyqxmd.com/read/28427206/mir-146a-and-mir-146b-promote-proliferation-migration-and-invasion-of-follicular-thyroid-carcinoma-via-inhibition-of-st8sia4
#1
Wei Ma, Xuzi Zhao, Leilei Liang, Guangzhi Wang, Yanyan Li, Xiaolong Miao, Yongfu Zhao
Follicular thyroid carcinoma (FTC) is a more aggressive form of thyroid cancer than the common papillary type. Alpha-2,8-sialyltransferase (ST8SIA) family members are expressed in various cancers and may be associated with FTC progression. In this study, we measured ST8SIA family expression in two FTC cell lines with different invasive potentials (FTC-133 and FTC-238) and Nthy-ori 3-1 cell lines, as well as FTC and normal thyroid tissues. ST8SIA4 was downregulated in the highly invasive FTC-238 cells and FTC tissues...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423672/%C3%AE-2-3-sialyltransferase-type-i-regulates-migration-and-peritoneal-dissemination-of-ovarian-cancer-cells
#2
Kuo-Chang Wen, Pi-Lin Sung, Shie-Liang Hsieh, Yu-Ting Chou, Oscar Kuang-Sheng Lee, Cheng-Wen Wu, Peng-Hui Wang
Epithelial ovarian cancer (EOC) has the highest mortality rate among gynecologic cancers due to advanced stage presentation, peritoneal dissemination, and refractory ascites at diagnosis. We investigated the role of α2,3-sialyltransferase type I (ST3GalI) by analyzing human ovarian cancer datasets and human EOC tissue arrays. We found that high expression of ST3GalI was associated with advanced stage EOC. Transwell migration and cell invasion assays showed that high ST3GalI expression enhanced migration of EOC cells...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413949/the-intrinsic-relationship-between-structure-and-function-of-the-sialyltransferase-st8sia-family-members
#3
Ri-Bo Huang, D Cheng, Bo Lu, S M Liao, Frederic A Troy Ii, Guo-Ping Zhou
As a subset of glycosyltransferases, the family of sialyltransferases catalyze transfer of sialic acid (Sia) residues to terminal non-reducing positions on oligosaccharide chains of glycoproteins and glycolipids, utilizing CMP-Neu5Ac as the activated sugar nucleotide donor. In the four known sialyltransferase families (ST3Gal, ST6Gal, ST6GalNAc and ST8Sia), the ST8Sia family catalyzes synthesis of si,8-linked sialic/polysialic acid (polySia) chains according to their acceptor specificity. We have determined 3D structural models of the ST8Sia family members, designated ST8Sia I(1), II(2), IV(4), V(5), and VI(6) using the Phyre2 server...
April 14, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28413120/endosome-to-trans-golgi-network-transport-of-proprotein-convertase-7-is-mediated-by-a-cluster-of-basic-amino-acids-and-palmitoylated-cysteines
#4
Jeroen Declercq, Bruno Ramos-Molina, Ragna Sannerud, Bas Brouwers, Vincent P E G Pruniau, Sandra Meulemans, Evelyn Plets, Wim Annaert, John W M Creemers
Proprotein Convertase 7 (PC7) is a Furin-like endoprotease that cleaves precursor proteins at basic amino acids. PC7 is concentrated in the trans-Golgi network (TGN) but it shuttles between the plasma membrane and the TGN depending on sequences in the cytoplasmic tail. A short region containing a three amino acids motif, P(724)-L(725)-C(726), is essential and sufficient for internalization of PC7 but not for TGN localization, which requires the additional presence of the juxtamembrane region. In this study we have investigated the contribution of a cluster of basic amino acids and two reversibly palmitoylated cysteine residues to endocytic trafficking...
April 7, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28395125/probing-the-cmp-sialic-acid-donor-specificity-of-two-human-%C3%AE-d-galactoside-sialyltransferases-st3gal-i-and-st6gal-i-selectively-acting-on-o-and-n-glycosylproteins
#5
Maxence Noel, Pierre-André Gilormini, Virginie Cogez, Nao Yamakawa, Dorothée Vicogne, Cédric Lion, Christophe Biot, Yann Guerardel, Anne Harduin-Lepers
Sialylation of glycoproteins and glycolipids catalyzed by sialyltransferases are enzymatic reactions taking place in the Golgi of mammalian cells whereby sialic acid residues are added at the non-reducing ends of oligosaccharides. Because sialylated glycans play critical roles in a number of human physio-pathological processes, the past two decades have witnessed the development of modified sialic acid derivatives for a better understanding of sialic acid biology and development of new therapeutic targets. However, nothing is known about how individual mammalian sialyltransferases tolerate and behave towards these unnatural CMP-sialic acid donors...
April 10, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28382513/rna-splicing-and-splicing-regulator-changes-in-prostate-cancer-pathology
#6
REVIEW
Jennifer Munkley, Karen Livermore, Prabhakar Rajan, David J Elliott
Changes in mRNA splice patterns have been associated with key pathological mechanisms in prostate cancer progression. The androgen receptor (abbreviated AR) transcription factor is a major driver of prostate cancer pathology and activated by androgen steroid hormones. Selection of alternative promoters by the activated AR can critically alter gene function by switching mRNA isoform production, including creating a pro-oncogenic isoform of the normally tumour suppressor gene TSC2. A number of androgen-regulated genes generate alternatively spliced mRNA isoforms, including a prostate-specific splice isoform of ST6GALNAC1 mRNA...
April 5, 2017: Human Genetics
https://www.readbyqxmd.com/read/28367091/disialyl-gd2-ganglioside-suppresses-icam-1-mediated-invasiveness-in-human-breast-cancer-mda-mb231-cells
#7
Kyung-Min Kwon, Tae-Wook Chung, Choong-Hwan Kwak, Hee-Jung Choi, Kyung-Woon Kim, Sun-Hyung Ha, Seung-Hak Cho, Young-Choon Lee, Ki-Tae Ha, Moon-Jo Lee, Cheorl-Ho Kim
The disialoganglioside GD3 has been considered to be involved in tumor progression or suppression in various tumor cells. However, the significance of the biological functions of GD3 in breast cancer cells is still controversial. This prompted us to study the possible relationship(s) between GD3 expression and the metastatic potential of a breast cancer MDA-MB231 cells as an estrogen receptor negative (ER-) type. The human GD3 synthase cDNA was transfected into MDA-MB231 cells, and G-418 bulk selection was used to select cells stably overexpressing the GD3 synthase...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28358117/altered-neo-lacto-series-glycolipid-biosynthesis-impairs-%C3%AE-2-6-sialylation-on-n-glycoproteins-in-ovarian-cancer-cells
#8
Shahidul Alam, Merrina Anugraham, Yen-Lin Huang, Reto S Kohler, Timm Hettich, Katharina Winkelbach, Yasmin Grether, Mónica Núñez López, Nailia Khasbiullina, Nicolai V Bovin, Götz Schlotterbeck, Francis Jacob
The (neo-) lacto series glycosphingolipids (nsGSLs) comprise of glycan epitopes that are present as blood group antigens, act as primary receptors for human pathogens and are also increasingly associated with malignant diseases. Beta-1, 3-N-acetyl-glucosaminyl-transferase 5 (B3GNT5) is suggested as the key glycosyltransferase for the biosynthesis of nsGSLs. In this study, we investigated the impact of CRISPR-Cas9 -mediated gene disruption of B3GNT5 (∆B3GNT5) on the expression of glycosphingolipids and N-glycoproteins by utilizing immunostaining and glycomics-based PGC-UHPLC-ESI-QTOF-MS/MS profiling...
March 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28351515/the-expression-of-sialyltransferases-is-regulated-by-the-bioavailability-and-biosynthesis-of-sialic-acids
#9
Kaya Bork, Wenke Weidemann, Beatrice Berneck, Magdalena Kuchta, Dorit Bennmann, Annett Thate, Otmar Huber, Vinayaga S Gnanapragassam, Rüdiger Horstkorte
Glycosylation is the most frequent and important post-translational modification of proteins. It occurs on specific consensus sequences but the final structure of a particular glycan is not coded on the DNA, rather it depends on the expression of the required enzymes and the availability of substrates (activated monosaccharides). Sialic acid (Sia) is the terminal monosaccharide of most glycoproteins or glycolipids (= glycoconjugates) and involved in a variety of function on molecular (e.g. determination of protein stability and half-life) and cellular level (e...
January 2017: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/28334934/a-pseudaminic-acid-or-a-legionaminic-acid-derivative-transferase-is-strain-specifically-implicated-in-the-general-protein-o-glycosylation-system-of-the-periodontal-pathogen-tannerella-forsythia
#10
Markus B Tomek, Bettina Janesch, Daniel Maresch, Markus Windwarder, Friedrich Altmann, Paul Messner, Christina Schäffer
The occurrence of nonulosonic acids in bacteria is wide-spread and linked to pathogenicity. However, the knowledge of cognate nonulosonic acid transferases is scarce. In the periodontopathogen Tannerella forsythia, several proposed virulence factors carry strain-specifically either a pseudaminic or a legionaminic acid derivative as terminal sugar on an otherwise structurally identical, protein-bound oligosaccharide. This study aims to shed light on the transfer of either nonulosonic acid derivative on a proximal N-acetylmannosaminuronic acid residue within the O-glycan structure, exemplified with the bacterium's abundant S-layer glycoproteins...
March 16, 2017: Glycobiology
https://www.readbyqxmd.com/read/28259967/enhanced-expression-of-%C3%AE-2-3-linked-sialic-acids-promotes-gastric-cancer-cell-metastasis-and-correlates-with-poor-prognosis
#11
Li Shen, Zhiguo Luo, Junbo Wu, Li Qiu, Ming Luo, Qing Ke, Xiaoxia Dong
Gastric cancer (GC) is a highly metastatic disease and one of the leading causes of cancer death in the world. Aberrant glycosylation is one of many molecular changes that accompany malignant transformation. This study was aimed at identification of glycan profiling changes in GC progression and its potential mechanisms. We employed a microarray with 91 lectins to compare the differential glycans in the three human GC cell lines, SGC-7901, BGC-823 and MGC-803. According to glycan-binding specificities of lectins, all GC cell lines expressed common sugar structures, such as mannose, galactose and fucose...
February 20, 2017: International Journal of Oncology
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
#12
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
#13
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
#14
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 the 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 15, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28154177/the-glycosyltransferase-st6gal-i-protects-tumor-cells-against-serum-growth-factor-withdrawal-by-enhancing-survival-signaling-and-proliferative-potential
#15
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 this study, we report a novel glycosylation-dependent mechanism that protects tumor cells from serum growth factor withdrawal. Our results suggest that the β-galactoside α-2,6-sialyltransferase 1 (ST6Gal-I) sialyltransferase, which is up-regulated 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 prosurvival signaling molecules, including pAkt, p-p70S6K, and pNFκB...
March 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28138383/systematic-chemoenzymatic-synthesis-of-o-sulfated-sialyl-lewis-x-antigens
#16
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
#17
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 multocidaα2-3-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...
February 21, 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
#18
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
#19
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
#20
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
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