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fucosyltransferase

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https://www.readbyqxmd.com/read/28530709/recognition-of-egf-like-domains-by-the-notch-modifying-o-fucosyltransferase-pofut1
#1
Zhijie Li, Kristina Han, John E Pak, Malathy Satkunarajah, Dongxia Zhou, James M Rini
Protein O-fucosyltransferase 1 (POFUT1) fucosylates the epidermal growth factor (EGF)-like domains found in cell-surface and secreted glycoproteins including Notch and its ligands. Although Notch fucosylation is critical for development, and POFUT1 deficiency leads to human disease, how this enzyme binds and catalyzes the fucosylation of its diverse EGF-like domain substrates has not been determined. Reported here is the X-ray crystal structure of mouse POFUT1 in complex with several EGF-like domains, including EGF12 and EGF26 of Notch...
May 22, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28483669/mechanisms-of-pulmonary-fibrosis-induced-by-core-fucosylation-in-pericytes
#2
Wei Sun, HaiYing Tang, Lili Gao, Xiuna Sun, Jia Liu, WeiDong Wang, Taihua Wu, Hongli Lin
Pulmonary fibrosis is a common outcome of a variety of pulmonary interstitial diseases, and myofibroblasts are the main culprit for this process. Recent studies have found that pericytes are one of the major sources of myofibroblasts; the transformation of which involves a complex process of activation of TGF-β/Smad2/3 and PDGFβ/Erk signaling pathways. We have reported that the transforming growth factor-β receptor and platelet-derived growth factor-β receptor (TGF-βR I and PDGFβR, respectively) are modified by glycosylation...
May 5, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28481220/mrna-mediated-glycoengineering-ameliorates-deficient-homing-of-human-stem-cell-derived-hematopoietic-progenitors
#3
Jungmin Lee, Brad Dykstra, Joel A Spencer, Laurie L Kenney, Dale L Greiner, Leonard D Shultz, Michael A Brehm, Charles P Lin, Robert Sackstein, Derrick J Rossi
Generation of functional hematopoietic stem and progenitor cells (HSPCs) from human pluripotent stem cells (PSCs) has been a long-sought-after goal for use in hematopoietic cell production, disease modeling, and eventually transplantation medicine. Homing of HSPCs from bloodstream to bone marrow (BM) is an important aspect of HSPC biology that has remained unaddressed in efforts to derive functional HSPCs from human PSCs. We have therefore examined the BM homing properties of human induced pluripotent stem cell-derived HSPCs (hiPS-HSPCs)...
May 8, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28440416/fuca1-is-induced-by-wild-type-p53-and-expressed-at-different-levels-in-thyroid-cancers-depending-on-p53-status
#4
Nobuo Tsuchida, Masa-Aki Ikeda, Υoshizumu Ιshino, Michele Grieco, Giancarlo Vecchio
Fucose residues of cell surface glycans, which play important roles in growth, invasion and metastasis, are added by fucosyltransferases (FUTs) and removed by α-L-fucosidases (FUCAs). By the differential display method, we isolated a 3' non-coding region of α-L-fucosidase-1 (FUCA1) (a gene coding for the lysosomal fucosidase-1 enzyme) as a wild-type p53-inducible gene: 18S and 20S FUCA1 mRNA species were induced in Saos-2 cells transfected with a temperature-sensitive p53 mutant at the permissive temperature...
April 20, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28430973/biological-functions-of-fucose-in-mammals
#5
Michael Schneider, Esam Al-Shareffi, Robert S Haltiwanger
Fucose is a 6-deoxy hexose in the L-configuration found in a large variety of different organisms. In mammals, fucose is incorporated into N-glycans, O-glycans and glycolipids by thirteen fucosyltransferases, all of which utilize the nucleotide charged form, GDP-fucose, to modify targets. Three of the fucosyltransferases, FUT8, FUT12/POFUT1, and FUT13/POFUT2, are essential for proper development in mice. Fucose modifications have also been implicated in many other biological functions including immunity and cancer...
April 18, 2017: Glycobiology
https://www.readbyqxmd.com/read/28423676/tumor-associated-macrophages-promote-ezrin-phosphorylation-mediated-epithelial-mesenchymal-transition-in-lung-adenocarcinoma-through-fut4-ley-up-regulation
#6
Aman Wang, Chang Lu, Zhen Ning, Wei Gao, Yunpeng Xie, Ningning Zhang, Jinxiao Liang, Faisal S Abbasi, Qiu Yan, Jiwei Liu
Tumor-associated macrophages (TAMs) are key components of tumor microenvironment (TME) during tumorigenesis and progression. However, the role of TAMs in lung adenocarcinoma is still unclear. In this study, we aimed to clarify the mechanism underlying the crosstalk between TAMs and epithelial-mesenchymal transition (EMT) of lung adenocarcinoma. Fucosyltransferase IV (FUT4) and its synthetic cancer sugar antigen Lewis Y (LeY) was aberrantly elevated in various solid tumors, it plays critical role in the invasion and metastasis...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28407380/n-glycan-maturation-mutants-in-lotus-japonicus-for-basic-and-applied-glycoprotein-research
#7
Carina T Pedersen, Ian Loke, Andrea Lorentzen, Sara Wolf, Manoj Kamble, Sebastian K Kristensen, David Munch, Simona Radutoiu, Edzard Spillner, Peter Roepstorff, Morten Thaysen-Andersen, Jens Stougaard, Svend Dam
Studies of protein N-glycosylation are important for answering fundamental questions on the diverse functions of glycoproteins in plant growth and development. Here we generated and characterised a comprehensive collection of Lotus japonicus LORE1 insertion mutants, each lacking the activity of one of the twelve enzymes required for normal N-glycan maturation in the glycosylation machinery. The inactivation of the individual genes resulted in altered N-glycan patterns as documented using mass spectrometry and glycan-recognising antibodies, indicating successful identification of null-mutations in the target glyco-genes...
April 13, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28396675/inactivation-of-the-%C3%AE-1-2-xylosyltransferase-and-the-%C3%AE-1-3-fucosyltransferase-genes-in-nicotiana-tabacum-by-2-cells-by-a-multiplex-crispr-cas9-strategy-results-in-glycoproteins-without-plant-specific-glycans
#8
Sébastien Mercx, Nicolas Smargiasso, François Chaumont, Edwin De Pauw, Marc Boutry, Catherine Navarre
Plants or plant cells can be used to produce pharmacological glycoproteins such as antibodies or vaccines. However these proteins carry N-glycans with plant-typical residues [β(1,2)-xylose and core α(1,3)-fucose], which can greatly impact the immunogenicity, allergenicity, or activity of the protein. Two enzymes are responsible for the addition of plant-specific glycans: β(1,2)-xylosyltransferase (XylT) and α(1,3)-fucosyltransferase (FucT). Our aim consisted of knocking-out two XylT genes and four FucT genes (12 alleles altogether) in Nicotiana tabacum BY-2 suspension cells using CRISPR/Cas9...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28371609/trastuzumab-and-pertuzumab-plant-biosimilars-modification-of-asn297-linked-glycan-of-the-mabs-produced-in-a-plant-with-fucosyltransferase-and-xylosyltransferase-gene-knockouts
#9
T V Komarova, E V Sheshukova, E N Kosobokova, M V Serebryakova, V S Kosorukov, V N Tashlitsky, Y L Dorokhov
Plant biosimilars of anticancer therapeutic antibodies are of interest not only because of the prospects of their practical use, but also as an instrument and object for study of plant protein glycosylation. In this work, we first designed a pertuzumab plant biosimilar (PPB) and investigated the composition of its Asn297-linked glycan in comparison with trastuzumab plant biosimilar (TPB). Both biosimilars were produced in wild-type (WT) Nicotiana benthamiana plant (PPB-WT and TPB-WT) and transgenic ΔXTFT N...
April 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28334865/structure-of-human-pofut1-its-requirement-in-ligand-independent-oncogenic-notch-signaling-and-functional-effects-of-dowling-degos-mutations
#10
Brian J McMillan, Brandon Zimmerman, Emily D Egan, Michael Lofgren, Xiang Xu, Anthony Hesser, Stephen C Blacklow
Protein O-fucosyltransferase-1 (POFUT1), which transfers fucose residues to acceptor sites on serine and threonine residues of epidermal growth factor-like repeats of recipient proteins, is essential for Notch signal transduction in mammals. Here, we examine the consequences of POFUT1 loss on the oncogenic signaling associated with certain leukemia-associated mutations of human Notch1, report the structures of human POFUT1 in free and GDP-fucose bound states, and assess the effects of Dowling-Degos mutations on human POFUT1 function...
March 17, 2017: Glycobiology
https://www.readbyqxmd.com/read/28334792/gwas-identifies-population-specific-new-regulatory-variants-in-fut6-associated-with-plasma-b12-concentrations-in-indians
#11
Suraj S Nongmaithem, Charudatta V Joglekar, Ghattu V Krishnaveni, Sirazul A Sahariah, Meraj Ahmad, Swetha Ramachandran, Meera Gandhi, Harsha Chopra, Anand Pandit, Ramesh D Potdar, Caroline Hd Fall, Chittaranjan S Yajnik, Giriraj R Chandak
Vitamin B12 is an important cofactor in one-carbon metabolism whose dysregulation is associated with various clinical conditions. Indians have a high prevalence of B12 deficiency but little is known about the genetic determinants of circulating B12 concentrations in Indians. We performed a genome-wide association study in 1001 healthy participants in the Pune Maternal Nutrition Study (PMNS), replication studies in 3418 individuals from other Indian cohorts and by meta-analysis identified new variants, rs3760775 (p = 1...
February 27, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28332312/antitumor-activity-of-chlpmab-2-a-human-mouse-chimeric-cancer-specific-antihuman-podoplanin-antibody-via-antibody-dependent-cellular-cytotoxicity
#12
Mika K Kaneko, Shinji Yamada, Takuro Nakamura, Shinji Abe, Yasuhiko Nishioka, Akiko Kunita, Masashi Fukayama, Yuki Fujii, Satoshi Ogasawara, Yukinari Kato
Human podoplanin (hPDPN), a platelet aggregation-inducing transmembrane glycoprotein, is expressed in different types of tumors, and it binds to C-type lectin-like receptor 2 (CLEC-2). The overexpression of hPDPN is involved in invasion and metastasis. Anti-hPDPN monoclonal antibodies (mAbs) such as NZ-1 have shown antitumor and antimetastatic activities by binding to the platelet aggregation-stimulating (PLAG) domain of hPDPN. Recently, we developed a novel mouse anti-hPDPN mAb, LpMab-2, using the cancer-specific mAb (CasMab) technology...
April 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28287404/mutations-in-%C3%AE-secretase-subunit-encoding-psenen-underlie-dowling-degos-disease-associated-with-acne-inversa
#13
Damian J Ralser, F Buket Ü Basmanav, Aylar Tafazzoli, Jade Wititsuwannakul, Sarah Delker, Sumita Danda, Holger Thiele, Sabrina Wolf, Michélle Busch, Susanne A Pulimood, Janine Altmüller, Peter Nürnberg, Didier Lacombe, Uwe Hillen, Jörg Wenzel, Jorge Frank, Benjamin Odermatt, Regina C Betz
Dowling-Degos disease (DDD) is an autosomal-dominant disorder of skin pigmentation associated with mutations in keratin 5 (KRT5), protein O-fucosyltransferase 1 (POFUT1), or protein O-glucosyltransferase 1 (POGLUT1). Here, we have identified 6 heterozygous truncating mutations in PSENEN, encoding presenilin enhancer protein 2, in 6 unrelated patients and families with DDD in whom mutations in KRT5, POFUT1, and POGLUT1 have been excluded. Further examination revealed that the histopathologic feature of follicular hyperkeratosis distinguished these 6 patients from previously studied individuals with DDD...
April 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28286292/metabolic-engineering-of-escherichia-coli-for-the-production-of-2-fucosyllactose-and-3-fucosyllactose-through-modular-pathway-enhancement
#14
Di Huang, Kexin Yang, Jia Liu, Yingying Xu, Yuanyuan Wang, Ru Wang, Bin Liu, Lu Feng
Fucosyllactoses, including 2'-fucosyllactose (2'-FL) and 3-fucosyllactose (3-FL), are important oligosaccharides in human milk that are commonly used as nutritional additives in infant formula due to their biological functions, such as the promotion of bifidobacteria growth, inhibition of pathogen infection, and improvement of immune response. In this study, we developed a synthetic biology approach to promote the efficient biosynthesis of 2'-FL and 3-FL in engineered Escherichia coli. To boost the production of 2'-FL and 3-FL, multiple modular optimization strategies were applied in a plug-and-play manner...
March 9, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28284868/development-of-%C3%AE-1-6-fucosyltransferase-inhibitors-through-the-diversity-oriented-syntheses-of-gdp-fucose-mimics-using-the-coupling-between-alkyne-and-sulfonyl-azide
#15
Yoshiyuki Manabe, Satomi Kasahara, Yohei Takakura, Xiaoxiao Yang, Shinji Takamatsu, Yoshihiro Kamada, Eiji Miyoshi, Daisuke Yoshidome, Koichi Fukase
We developed α1,6-fucosyltransferase (FUT8) inhibitors through a diversity-oriented synthesis. The coupling reaction between the fucose unit containing alkyne and the guanine unit containing sulfonyl azide under various conditions afforded a series of Guanosine 5'-diphospho-β-l-fucose (GDP-fucose) analogs. The synthesized compounds displayed FUT8 inhibition activity. A docking study revealed that the binding mode of the inhibitor synthesized with FUT8 was similar to that of GDP-fucose.
February 28, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28267695/potential-biomarkers-in-lewis-negative-patients-with-pancreatic-cancer
#16
Guopei Luo, Chen Liu, Meng Guo, He Cheng, Yu Lu, Kaizhou Jin, Liang Liu, Jiang Long, Jin Xu, Renquan Lu, Quanxing Ni, Xianjun Yu
OBJECTIVE: To examine potential biomarkers in Lewis negative patients with pancreatic cancer. BACKGROUND: Carbohydrate antigen 19-9 (CA19-9) is currently the most important and widely used biomarker in pancreatic cancer. However, approximately 5 to 10% of the population are Lewis negative individuals, and they are documented to have scarce or no CA19-9 secretion. Therefore, it is necessary to explore potential biomarkers to compensate for this drawback. METHODS: Lewis genotypes were determined in a large cohort of patients with pancreatic cancer (682 cases) and controls (525 cases) by sequencing the Fucosyltransferase 3 (FUT3) gene from genomic DNA...
April 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28265002/deletion-of-pofut1-in-mouse-skeletal-myofibers-induces-muscle-aging-related-phenotypes-in-cis-and-in-trans
#17
Deborah A Zygmunt, Neha Singhal, Mi-Lyang Kim, Megan L Cramer, Kelly E Crowe, Rui Xu, Ying Jia, Jessica Adair, Isabel Martinez-Pena Y Valenzuela, Mohammed Akaaboune, Peter White, Paulus M Janssen, Paul T Martin
Sarcopenia, the loss of muscle mass and strength during normal aging, involves coordinate changes in skeletal myofibers and the cells that contact them, including satellite cells and motor neurons. Here we show that the protein O-fucosyltransferase 1 gene (Pofut1), which encodes a glycosyltransferase required for NotchR-mediated cell-cell signaling, has reduced expression in aging skeletal muscle. Moreover, premature postnatal deletion of Pofut1 in skeletal myofibers can induce aging-related phenotypes in cis within skeletal myofibers and in trans within satellite cells and within motor neurons via the neuromuscular junction...
May 15, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28261212/%C3%AE-2%C3%A2-1-fructans-modulate-the-immune-system-in-vivo-in-a-microbiota-dependent-and%C3%A2-independent-fashion
#18
Floris Fransen, Neha M Sahasrabudhe, Marlies Elderman, Margaret Bosveld, Sahar El Aidy, Floor Hugenholtz, Theo Borghuis, Ben Kousemaker, Simon Winkel, Christa van der Gaast-de Jongh, Marien I de Jonge, Mark V Boekschoten, Hauke Smidt, Henk A Schols, Paul de Vos
It has been shown in vitro that only specific dietary fibers contribute to immunity, but studies in vivo are not conclusive. Here, we investigated degree of polymerization (DP) dependent effects of β2→1-fructans on immunity via microbiota-dependent and -independent effects. To this end, conventional or germ-free mice received short- or long-chain β2→1-fructan for 5 days. Immune cell populations in the spleen, mesenteric lymph nodes (MLNs), and Peyer's patches (PPs) were analyzed with flow cytometry, genome-wide gene expression in the ileum was measured with microarray, and gut microbiota composition was analyzed with 16S rRNA sequencing of fecal samples...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28244988/the-arabidopsis-o-fucosyltransferase-spindly-activates-nuclear-growth-repressor-della
#19
Rodolfo Zentella, Ning Sui, Benjamin Barnhill, Wen-Ping Hsieh, Jianhong Hu, Jeffrey Shabanowitz, Michael Boyce, Neil E Olszewski, Pei Zhou, Donald F Hunt, Tai-Ping Sun
Plant development requires coordination among complex signaling networks to enhance the plant's adaptation to changing environments. DELLAs, transcription regulators originally identified as repressors of phytohormone gibberellin signaling, play a central role in integrating multiple signaling activities via direct protein interactions with key transcription factors. Here, we found that DELLA is mono-O-fucosylated by the novel O-fucosyltransferase SPINDLY (SPY) in Arabidopsis thaliana. O-fucosylation activates DELLA by promoting its interaction with key regulators in brassinosteroid- and light-signaling pathways, including BRASSINAZOLE-RESISTANT1 (BZR1), PHYTOCHROME-INTERACTING-FACTOR3 (PIF3) and PIF4...
May 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28229927/alteration-of-n-glycan-expression-profile-and-glycan-pattern-of-glycoproteins-in-human-hepatoma-cells-after-hcv-infection
#20
Tian Xiang, Ganglong Yang, Xiaoyu Liu, Yidan Zhou, Zhongxiao Fu, Fangfang Lu, Jianguo Gu, Naoyuki Taniguchi, Zengqi Tan, Xi Chen, Yan Xie, Feng Guan, Xiao-Lian Zhang
BACKGROUND: Hepatitis C virus (HCV) infection causes chronic liver diseases, liver fibrosis and even hepatocellular carcinoma (HCC). However little is known about any information of N-glycan pattern in human liver cell after HCV infection. METHODS: The altered profiles of N-glycans in HCV-infected Huh7.5.1 cell were analyzed by using mass spectrometry. Then, lectin microarray, lectin pull-down assay, reverse transcription-quantitative real time PCR (RT-qPCR) and western-blotting were used to identify the altered N-glycosylated proteins and glycosyltransferases...
February 14, 2017: Biochimica et Biophysica Acta
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