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https://www.readbyqxmd.com/read/28808029/elucidating-crosstalk-mechanisms-between-phosphorylation-and-o-glcnacylation
#1
Aneika C Leney, Dris El Atmioui, Wei Wu, Huib Ovaa, Albert J R Heck
Proteins can be modified by multiple posttranslational modifications (PTMs), creating a PTM code that controls the function of proteins in space and time. Unraveling this complex PTM code is one of the great challenges in molecular biology. Here, using mass spectrometry-based assays, we focus on the most common PTMs-phosphorylation and O-GlcNAcylation-and investigate how they affect each other. We demonstrate two generic crosstalk mechanisms. First, we define a frequently occurring, very specific and stringent phosphorylation/O-GlcNAcylation interplay motif, (pSp/T)P(V/A/T)(gS/gT), whereby phosphorylation strongly inhibits O-GlcNAcylation...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28802580/suppressive-role-of-ogt-mediated-o-glcnacylation-of-bap1-in-retinoic-acid-signaling
#2
Seungtae Moon, Yong-Kyu Lee, Sang-Wang Lee, Soo-Jong Um
BRCA1-associated protein 1 (BAP1) has been implicated in diverse biological functions, including tumor suppression. However, its regulation via glycosylation and its role in embryonic stem (ES) cells are poorly defined. BAP1 was recently reported to interact with O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT). Here, we confirmed the physical interaction and investigated its functional significance. The O-GlcNAcylation of BAP1, which requires OGT, was examined in vivo and in vitro, and was proven using alloxan, an OGT inhibitor...
August 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28793197/glycosylation-with-o-linked-%C3%AE-n-acetylglucosamine-o-glcnac-induces-vascular-dysfunction-via-production-of-superoxide-anion-reactive-oxygen-species
#3
Leonardo Souza-Silva, Rhéure Alves-Lopes, Jéssica Silva Miguez, Vanessa Dela Justina, Karla Bianca Neves, Fabíola Leslie Mestriner, Rita C Tostes, Fernanda Regina Giachini, Victor V Lima
Overproduction of superoxide anion (•O2-) and O-linked β-N-acetylglucosamine (O-GlcNAc)-modification in the vascular system are contributors to endothelial dysfunction. This study tested the hypothesis that increased levels of O-GlcNAc-modified proteins contribute to •O2- production via activation of NADPH oxidase, resulting in impaired vasodilation. Rat aortic segments and vascular smooth muscle cell (VSMCs) were incubated with vehicle (methanol) or PUGNAc (100 µM). PUGNAc produced a time-dependent increase in O-GlcNAc levels in VSMC and decreased endothelium-dependent relaxation, which was prevented by apocynin and Tiron, suggesting that •O2- contributes to endothelial dysfunction under augmented O-GlcNAc levels...
August 9, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28768194/a-conserved-splicing-silencer-dynamically-regulates-o-glcnac-transferase-intron-retention-and-o-glcnac-homeostasis
#4
Sung-Kyun Park, Xiaorong Zhou, Kathryn E Pendleton, Olga V Hunter, Jennifer J Kohler, Kathryn A O'Donnell, Nicholas K Conrad
Modification of nucleocytoplasmic proteins with O-GlcNAc regulates a wide variety of cellular processes and has been linked to human diseases. The enzymes O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) add and remove O-GlcNAc, but the mechanisms regulating their expression remain unclear. Here, we demonstrate that retention of the fourth intron of OGT is regulated in response to O-GlcNAc levels. We further define a conserved intronic splicing silencer (ISS) that is necessary for OGT intron retention. Deletion of the ISS in colon cancer cells leads to increases in OGT, but O-GlcNAc homeostasis is maintained by concomitant increases in OGA protein...
August 1, 2017: Cell Reports
https://www.readbyqxmd.com/read/28760965/quantitative-time-resolved-chemoproteomics-reveals-that-stable-o-glcnac-regulates-box-c-d-snornp-biogenesis
#5
Wei Qin, Pinou Lv, Xinqi Fan, Baiyi Quan, Yuntao Zhu, Ke Qin, Ying Chen, Chu Wang, Xing Chen
O-linked GlcNAcylation (O-GlcNAcylation), a ubiquitous posttranslational modification on intracellular proteins, is dynamically regulated in cells. To analyze the turnover dynamics of O-GlcNAcylated proteins, we developed a quantitative time-resolved O-linked GlcNAc proteomics (qTOP) strategy based on metabolic pulse-chase labeling with an O-GlcNAc chemical reporter and stable isotope labeling with amino acids in cell culture (SILAC). Applying qTOP, we quantified the turnover rates of 533 O-GlcNAcylated proteins in NIH 3T3 cells and discovered that about 14% exhibited minimal removal of O-GlcNAc or degradation of protein backbones...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28760863/acute-increases-in-protein-o-glcnacylation-dampen-epileptiform-activity-in-hippocampus
#6
L T Stewart, A U Khan, K Wang, D Pizarro, S Pati, S C Buckingham, M L Olsen, J C Chatham, L L McMahon
O-GlcNAcylation is a ubiquitous and dynamic posttranslational modification involving the O-linkage of β-N-acetylglucosamine to serine/threonine residues of membrane, cytosolic, and nuclear proteins. This modification is similar to phosphorylation, and regarded as a key regulator of cell survival and homeostasis. Previous studies have shown that phosphorylation of serine residues on synaptic proteins is a major regulator of synaptic strength and long-term plasticity, suggesting O-GlcNAcylation of synaptic proteins is likely as important as phosphorylation; however, few studies have investigated its role in synaptic efficacy...
July 31, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28742148/hijacking-of-the-o-glcnaczyme-complex-by-the-htlv-1-tax-oncoprotein-facilitates-viral-transcription
#7
Damien Groussaud, Mostafa Khair, Armelle I Tollenaere, Laetitia Waast, Mei-Shiue Kuo, Marianne Mangeney, Christophe Martella, Yann Fardini, Solène Coste, Mouloud Souidi, Laurence Benit, Claudine Pique, Tarik Issad
The viral Tax oncoprotein plays a key role in both Human T-cell lymphotropic virus type 1 (HTLV-1)-replication and HTLV-1-associated pathologies, notably adult T-cell leukemia. Tax governs the transcription from the viral 5'LTR, enhancing thereby its own expression, via the recruitment of dimers of phosphorylated CREB to cAMP-response elements located within the U3 region (vCRE). In addition to phosphorylation, CREB is also the target of O-GlcNAcylation, another reversible post-translational modification involved in a wide range of diseases, including cancers...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28739801/sustained-o-glcnacylation-reprograms-mitochondrial-function-to-regulate-energy-metabolism
#8
Ee Phie Tan, Steven R McGreal, Stefan Graw, Robert Tessman, Scott J Koppel, Pramod Dhakal, Zhen Zhang, Miranda Machacek, Natasha E Zachara, Devin C Koestler, Kenneth R Peterson, John P Thyfault, Russell H Swerdlow, Partha Krishnamurthy, Luciano DiTacchio, Udayan Apte, Chad Slawson
Dysfunctional mitochondria and generation of reactive oxygen species (ROS) promote chronic diseases, which have spurred interest in the molecular mechanisms underlying these conditions. Previously, we have demonstrated that disruption of post-translational modification of proteins with β-linked N-acetylglucosamine (O-GlcNAcylation) via overexpression of the O-GlcNAc regulating enzymes O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) impairs mitochondrial function. Here, we report that sustained alterations in O-GlcNAcylation either by pharmacological or genetic manipulation also alters metabolic function...
July 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28724388/o-glcnac-regulation-of-autophagy-and-%C3%AE-synuclein-homeostasis-implications-for-parkinson-s-disease
#9
Willayat Y Wani, Xiaosen Ouyang, Gloria A Benavides, Matthew Redmann, Stacey S Cofield, John J Shacka, John C Chatham, Victor Darley-Usmar, Jianhua Zhang
Post-translational modification on protein Ser/Thr residues by O-linked attachment of ß-N-acetyl-glucosamine (O-GlcNAcylation) is a key mechanism integrating redox signaling, metabolism and stress responses. One of the most common neurodegenerative diseases that exhibit aberrant redox signaling, metabolism and stress response is Parkinson's disease, suggesting a potential role for O-GlcNAcylation in its pathology. To determine whether abnormal O-GlcNAcylation occurs in Parkinson's disease, we analyzed lysates from the postmortem temporal cortex of Parkinson's disease patients and compared them to age matched controls and found increased protein O-GlcNAcylation levels...
July 19, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28722313/cellular-glycosylation-senses-metabolic-changes-and-modulates-cell-plasticity-during-emt
#10
REVIEW
P Carvalho-Cruz, F Alisson-Silva, A R Todeschini, W B Dias
Epithelial to mesenchymal transition (EMT) is a developmental program reactivated by tumor cells that leads to the switch from epithelial to mesenchymal phenotype. During EMT, cells are transcriptionally regulated to decrease E-cadherin expression while expressing mesenchymal markers such as vimentin, fibronectin and N-cadherin. Growing body of evidences suggest that cells engaged in EMT undergo a metabolic reprograming process, redirecting glucose flux toward Hexosamine Biosynthesis Pathway (HBP) which fuels aberrant glycosylation patterns that are extensively observed in cancer cells...
July 19, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28713921/anti%C3%A2-lung-cancer-effect-of-glucosamine-by-suppressing-the-phosphorylation-of-foxo
#11
Zhanwu Yu, Yinghua Ju, Hongxu Liu
Lung cancer is the most common cause of cancer‑associated mortality worldwide, and glucosamine has the potential to exhibit antitumor activity. To reveal its anti‑lung cancer mechanism, the present study investigated the effect of glucosamine on the transcriptional activity of forkhead box O (FOXO)1 and FOXO3, and associated signal transduction pathways in A549 cells. An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28710799/high-glucose-induces-o-glcnac-glycosylation-of-the-vitamin-d-receptor-vdr-in-thp1-cells-and-in-human-macrophages-derived-from-monocytes
#12
Fernando Hernández-Sánchez, Silvia Guzmán-Beltrán, María Teresa Herrera, Yolanda Gonzalez, Manuel Salgado, Guadalupe Fabian, Martha Torres
Chronic hyperglycemia increases the carbon flux through the hexosamine pathway, allowing the accumulation of UDP-GlcNAc. UDP-GlcNAc is the sugar donor for the enzyme-mediated protein glycosylation event known as OGlcNAcylation. This posttranslational modification targets several transcription factors implicated in glucose toxicity, insulin resistance, and diabetes. Vitamin D plays an important role in glucose homeostasis and insulin secretion through transcriptional mechanisms mediated by its receptor (VDR)...
July 15, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28691313/moderate-mammalian-target-of-rapamycin-inhibition-induces-autophagy-in-htr8-svneo-cells-via-o-linked-%C3%AE-n-acetylglucosamine-signaling
#13
Qiuxia Zhang, Quan Na, Weiwei Song
AIM: Autophagy, a highly regulated process with a dual role (pro-survival or pro-death), has been implicated in adverse pregnancy outcomes. The aim of this study was to explore the mechanism whereby mammalian target of rapamycin (mTOR) signaling regulates autophagy by modulating protein O-GlcNAcylation in human trophoblasts. METHODS: HTR8/SVneo cells were incubated in serum-free medium for different time intervals or treated with varying doses of Torin1. Protein expression and cell apoptosis were detected by immunoblotting and flow cytometry, respectively...
July 10, 2017: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/28688099/increased-o-linked-n-acetylglucosamine-modification-of-nf-%C3%AE-b-and-augmented-cytokine-production-in-the-placentas-from-hyperglycemic-rats
#14
Vanessa Dela Justina, Jéssica S Gonçalves, Raiany Alves de Freitas, Adriany Dias Fonseca, Gustavo T Volpato, Rita C Tostes, Fernando S Carneiro, Victor Vitorino Lima, Fernanda R Giachini
Inflammation as a result of NF-κB activation may result from the classical (canonical) pathway, with disconnection of the IκB inhibitor and subsequent nuclear translocation or, alternatively, by post-translational modifications of modulatory proteins or NF-κB subunits (non-canonical pathway). We hypothesized that hyperglycemia-induced increased glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) of NF-κB in placental tissue leads to augmented production of pro-inflammatory cytokines, culminating in placental dysfunction and fetal restriction growth...
July 8, 2017: Inflammation
https://www.readbyqxmd.com/read/28686627/wga-based-lectin-affinity-gel-electrophoresis-a-novel-method-for-the-detection-of-o-glcnac-modified-proteins
#15
Yuji Kubota, Ko Fujioka, Mutsuhiro Takekawa
Post-translational modification with O-linked β-N-acetylglucosamine (O-GlcNAc) occurs selectively on serine and/or threonine residues of cytoplasmic and nuclear proteins, and dynamically regulates their molecular functions. Since conventional strategies to evaluate the O-GlcNAcylation level of a specific protein require time-consuming steps, the development of a rapid and easy method for the detection and quantification of an O-GlcNAcylated protein has been a challenging issue. Here, we describe a novel method in which O-GlcNAcylated and non-O-GlcNAcylated forms of proteins are separated by lectin affinity gel electrophoresis using wheat germ agglutinin (WGA), which primarily binds to N-acetylglucosamine residues...
2017: PloS One
https://www.readbyqxmd.com/read/28681591/o-glcnacylation-of-nf-%C3%AE%C2%BAb-promotes-lung-metastasis-of-cervical-cancer-cells-via-upregulation-of-cxcr4-expression
#16
Akhtar Ali, Sung Hwan Kim, Min Jun Kim, Mee Young Choi, Sang Soo Kang, Gyeong Jae Cho, Yoon Sook Kim, Jun-Young Choi, Wan Sung Choi
C-X-C chemokine receptor 4 (CXCR4) stimulates cancer metastasis. NF-κB regulates CXCR4 expression in cancer cells, and O-GlcNAc modification of NF-κB promotes its transcriptional activity. Here, we determined whether CXCR4 expression is affected by O-GlcNAcylation of NF-κB in lung metastasis of cervical cancer. We found elevated levels of O-linked-N-actylglucosamine transferase (OGT) and O-GlcNAcylation in cervical cancer cells compared to those in non-malignant epithelial cells and detected increased expression of NF-κB p65 (p65) and CXCR4 in cervical cancer cells...
July 31, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28670495/bitterness-in-sugar-o-glcnacylation-aggravates-pre-b-acute-lymphocytic-leukemia-through-glycolysis-via-the-pi3k-akt-c-myc-pathway
#17
Bing Zhang, Panpan Zhou, Xue Li, Qing Shi, Dong Li, Xiuli Ju
Abnormal cellular energetics has emerged as a hallmark of cancer cells. Deregulating aerobic glycolysis can alter multiple metabolic and signaling pathways in cancer cells, and trigger unlimited growth and proliferation. Accumulating evidence suggests that elevated levels of protein modification with β-N-acetylglucosamine (O-GlcNAcylation) along with dysregulation of O-GlcNAc transferase (OGT) and/or O-GlcNAcase (OGA) levels may act as a nutrient sensor in cancer cells. However, the underlying mechanism of O-GlcNAcylation and the relationship between O-GlcNAcylation and glycolysis are largely unknown in pre-B acute lymphocytic leukemia (pre-B-ALL)...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28669142/polymorphism-in-the-intron-20-of-porcine-o-linked-n-acetylglucosamine-transferase
#18
Jong Gug Kim, Dan Nonneman, Doo-Wan Kim, Sangsu Shin, Gary A Rohrer
OBJECTIVE: O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) catalyzes the addition of O-GlcNAc and GlcNAcylation has extensive crosstalk with phosphorylation to regulate signaling and transcription. Pig OGT is located near the region of chromosome X that affects follicle stimulating hormone level and testes size. The objective of this study was to find the variations of OGT between European and Chinese pigs. METHODS: Pigs were tested initially for polymorphism in OGT among European and Chinese pigs by polymerase chain reaction and sequencing at the U...
August 2017: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/28663241/glycosylation-of-keap1-links-nutrient-sensing-to-redox-stress-signaling
#19
Po-Han Chen, Timothy J Smith, Jianli Wu, Priscila F Siesser, Brittany J Bisnett, Farhan Khan, Maxwell Hogue, Erik Soderblom, Flora Tang, Jeffrey R Marks, Michael B Major, Benjamin M Swarts, Michael Boyce, Jen-Tsan Chi
O-GlcNAcylation is an essential, nutrient-sensitive post-translational modification, but its biochemical and phenotypic effects remain incompletely understood. To address this question, we investigated the global transcriptional response to perturbations in O-GlcNAcylation. Unexpectedly, many transcriptional effects of O-GlcNAc transferase (OGT) inhibition were due to the activation of NRF2, the master regulator of redox stress tolerance. Moreover, we found that a signature of low OGT activity strongly correlates with NRF2 activation in multiple tumor expression datasets...
August 1, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28661453/lxr%C3%AE-regulates-hepatic-chrebp%C3%AE-activity-and-lipogenesis-upon-glucose-but-not-fructose-feeding-in-mice
#20
Qiong Fan, Rikke C Nørgaard, Christian Bindesbøll, Christin Lucas, Knut Tomas Dalen, Eshrat Babaie, Harri M Itkonen, Jason Matthews, Hilde I Nebb, Line M Grønning-Wang
Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis. LXRα/β double knockout (LXRα(-/-)/β(-/-)) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis. However, the role of LXRs in fructose-induced ChREBP activation and lipogenesis is currently unknown...
June 29, 2017: Nutrients
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