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https://www.readbyqxmd.com/read/29352075/o-linked-%C3%AE-n-acetylglucosamine-o-glcnac-modification-a-new-pathway-to-decode-pathogenesis-of-diabetic-retinopathy
#1
REVIEW
Zafer Gurel, Nader Sheibani
The incidence of diabetes continues to rise among all ages and ethnic groups worldwide. Diabetic retinopathy (DR) is a complication of diabetes that affects the retinal neurovasculature causing serious vision problems, including blindness. Its pathogenesis and severity is directly linked to the chronic exposure to high glucose conditions. No treatments are currently available to stop the development and progression of DR. To develop new and effective therapeutic approaches, it is critical to better understand how hyperglycemia contributes to the pathogenesis of DR at the cellular and molecular levels...
January 31, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29351928/mapping-and-quantification-of-over-2-000-o-linked-glycopeptides-in-activated-human-t-cells-with-isotope-targeted-glycoproteomics-isotag
#2
Christina M Woo, Peder J Lund, Andrew C Huang, Mark M Davis, Carolyn R Bertozzi, Sharon Pitteri
Post-translational modifications (PTMs) on proteins often function to regulate signaling cascades, with the activation of T cells during an adaptive immune response being a classic example.  Mounting evidence indicates that the modification of proteins by O-linked N-acetylglucosamine (O-GlcNAc), the only mammalian glycan found on nuclear and cytoplasmic proteins, helps regulate T cell activation.  Yet, a mechanistic understanding of how O-GlcNAc functions in T cell activation remains elusive, partly because of the difficulties in mapping and quantifying O-GlcNAc sites...
January 19, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29337275/the-o-%C3%AE-linked-n-acetylglucosaminylation-of-the-lamin-b-receptor-and-its-impact-on-dna-binding-and-phosphorylation
#3
Caroline Smet-Nocca, Adeline Page, François-Xavier Cantrelle, Eleni Nikolakaki, Isabelle Landrieu, Thomas Giannakouros
Lamin B Receptor (LBR) is an integral protein of the interphase inner nuclear membrane that is implicated in chromatin anchorage to the nuclear envelope. Phosphorylation of a stretch of arginine-serine (RS) dipeptides in the amino-terminal nucleoplasmic domain of LBR regulates the interactions of the receptor with other nuclear proteins, DNA and RNA and thus modulates tethering of heterochromatin to the nuclear envelope. While phosphorylation has been extensively studied, very little is known about other post-translational modifications of the protein...
January 11, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29333477/notch-ligand-binding-assay-using-flow-cytometry
#4
Shweta Varshney, Pamela Stanley
Notch signaling is an evolutionary conserved signaling pathway that plays an indispensable role during development, and in the maintenance of homeostatic processes, in a wide variety of tissues (Kopan, 2012; Hori et al., 2013). The multifaceted roles of Notch signaling are stringently regulated at different levels. One of the most important aspects of regulation is the binding of different Notch ligands to each Notch receptor (NOTCH1-NOTCH4). Canonical ligands Delta or Serrate (in Drosophila), and Delta-like (DLL1 and DLL4) or Jagged (JAG1 and JAG2) (in mammals), are transmembrane glycoproteins...
December 5, 2017: Bio-protocol
https://www.readbyqxmd.com/read/29327476/o-glcnacylation-in-oral-squamous-cell-carcinoma
#5
Tassaporn Kongkaew, Win Pa Pa Aung, Chayarop Supanchart, Anupong Makeudom, Sarawat Langsa-Ard, Thanapat Sastraruji, Ponlatham Chaiyarit, Suttichai Krisanaprakornkit
BACKGROUND: Two post-translational mechanisms commonly demonstrated in various cancers are protein phosphorylation and glycosylation by O-linked β-N-acetylglucosamine (O-GlcNAc). However, only phosphorylation of the epidermal growth factor receptor (EGFR)/Akt pathway has been reported in oral squamous cell carcinoma (OSCC). Therefore, we aimed to determine both post-translational modifications in OSCC tissues and in oral cancer cells compared to normal tissues and oral keratinocytes and to find correlations of these modifications with histological grading...
January 11, 2018: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/29325178/modulation-of-o-glcnac-levels-in-the-liver-impacts-acetaminophen-induced-liver-injury-by-affecting-protein-adduct-formation-and-glutathione-synthesis
#6
Steven R McGreal, Bharat Bhushan, Chad Walesky, Mitchell R McGill, Margitta Lebofsky, Sylvie E Kandel, Robert D Winefield, Hartmut Jaeschke, Natasha E Zachara, Zhen Zhang, Ee Phie Tan, Chad Slawson, Udayan Apte
Overdose of acetaminophen (APAP) results in acute liver failure. We have investigated the role of a post-translational modification of proteins called O-GlcNAcylation, where the O-GlcNAc transferase (OGT) adds and O-GlcNAcase (OGA) removes a single β-D-N-acetylglucosamine (O-GlcNAc) moiety, in the pathogenesis of APAP-induced liver injury. Hepatocyte specific OGT knockout mice (OGT KO), which have reduced O-GlcNAcylation, and WT controls were treated with 300 mg/kg APAP and the development of injury was studied over a time course from 0-24 hr...
January 9, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29315243/conditions-inducing-excessive-o-glcnacylation-inhibit-bmp2-induced-osteogenic-differentiation-of-c2c12-cells
#7
Hanna Gu, Mina Song, Kanitsak Boonanantanasarn, Kyunghwa Baek, Kyung Mi Woo, Hyun-Mo Ryoo, Jeong-Hwa Baek
Hyperglycemic conditions in diabetic patients can affect various cellular functions, including the modulation of osteogenic differentiation. However, the molecular mechanisms by which hyperglycemia affects osteogenic differentiation are yet to be clarified. This study aimed to investigate whether the aberrant increase in protein O-linked-β-N-acetylglucosamine glycosylation (O-GlcNAcylation) contributes to the suppression of osteogenic differentiation due to hyperglycemia. To induce osteogenic differentiation, C2C12 cells were cultured in the presence of recombinant human bone morphogenetic protein 2 (BMP2)...
January 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29306432/methods-for-the-detection-study-and-dynamic-profiling-of-o-glcnac-glycosylation
#8
John W Thompson, Matthew E Griffin, Linda C Hsieh-Wilson
The addition of O-linked β-N-acetylglucosamine (O-GlcNAc) to serine/threonine residues of proteins is a ubiquitous posttranslational modification found in all multicellular organisms. Like phosphorylation, O-GlcNAc glycosylation (O-GlcNAcylation) is inducible and regulates a myriad of physiological and pathological processes. However, understanding the diverse functions of O-GlcNAcylation is often challenging due to the difficulty of detecting and quantifying the modification. Thus, robust methods to study O-GlcNAcylation are essential to elucidate its key roles in the regulation of individual proteins, complex cellular processes, and disease...
2018: Methods in Enzymology
https://www.readbyqxmd.com/read/29301793/o-glcnacylation-of-the-tumor-suppressor-foxo3-triggers-aberrant-cancer-cell-growth
#9
Heon Shin, Hyun-Jeong Cha, Keun Na, Min Jung Lee, Jin-Young Cho, Chae-Yeon Kim, Eun Kyung Kim, Chang Moo Kang, Hoguen Kim, Young-Ki Paik
Post-translational modifications of tumor suppressors can induce abnormal cell growth. Here we identify site-specific O-GlcNAcylation as a critical block of FOXO3 that may abrogate a part of the p53 pathway, resulting in aberrant cancer cell growth. Of seven O-GlcNAcylation sites identified within the FOXO3 transactivation domain, we found that changes in O-GlcNAcylation at Ser284 modulated p21-mediated cancer cell growth. Overexpression of either O-GlcNAcylated FOXO3 (FOX-OV) or a Ser-to-Ala mutant (S284A) in PANC-1 cells indicated that S284 O-GlcNAc acts as a critical block of the FOXO tumor suppressor and induces proliferation in PANC-1 cancer cells by stimulating the MDM2-p53-p21 axis...
January 4, 2018: Cancer Research
https://www.readbyqxmd.com/read/29279740/detection-of-o-linked-n-acetylglucosamine-modification-and-its-associated-enzymes-in-human-degenerated-intervertebral-discs
#10
Georgios Nikolaou, Aristeidis H Zibis, Apostolos H Fyllos, Antonios Katsioulis, Sotirios Sotiriou, Anastasios Kotrotsios, Markos Sgantzos, Aikaterini Vassiou, Dimitrios L Arvanitis
Study Design: Human herniated discs were obtained from discectomy specimens for the immunohistochemical detection of O-GlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase (OGT). Purpose: This study aimed to quantify the extent of O-GlcNAcylation and its associated enzymes (OGT/OGA) in human degenerated intervertebral discs. Overview of Literature: The O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications are currently the focus of extensive research...
December 2017: Asian Spine Journal
https://www.readbyqxmd.com/read/29249667/o-glcnac-on-pkc%C3%AE-inhibits-the-fgf4-pkc%C3%AE-mek-erk1-2-pathway-via-inhibition-of-pkc%C3%AE-phosphorylation-in-mouse-embryonic-stem-cells
#11
Taichi Miura, Masahiko Kume, Takeshi Kawamura, Kazuo Yamamoto, Takao Hamakubo, Shoko Nishihara
Mouse embryonic stem cells (ESCs) differentiate into multiple cell types during organismal development. Fibroblast growth factor 4 (FGF4) signaling induces differentiation from ESCs via the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2). The FGF4-MEK-ERK1/2 pathway is inhibited to maintain ESCs in the undifferentiated state. However, the inhibitory mechanism of the FGF4-MEK-ERK1/2 pathway in ESCs is uncharacterized...
December 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29249144/biosite-a-method-for-direct-detection-and-quantitation-of-site-specific-biotinylation
#12
Dae In Kim, Jevon A Cutler, Chan Hyun Na, Sina Reckel, Santosh Renuse, Anil K Madugundu, Raiha Tahir, Hana L Goldschmidt, Karen L Reddy, Richard L Huganir, Xinyan Wu, Natasha E Zachara, Oliver Hantschel, Akhilesh Pandey
Biotin-based labeling strategies are widely employed to study protein-protein interactions, subcellular proteomes and post-translational modifications, as well as, used in drug discovery. While the high affinity of streptavidin for biotin greatly facilitates the capture of biotinylated proteins, it still presents a challenge, as currently employed, for the recovery of biotinylated peptides. Here we describe a strategy designated Biotinylation Site Identification Technology (BioSITe) for the capture of biotinylated peptides for LC-MS/MS analyses...
December 28, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/29244071/the-glycosyltransferase-eogt-regulates-adropin-expression-in-decidualizing-human-endometrium
#13
Joanne Muter, Mohammad T Alam, Pavle Vrljicak, Flavio S V Barros, Peter T Ruane, Lauren J Ewington, John D Aplin, Melissa Westwood, Jan J Brosens
In pregnancy, resistance of endometrial decidual cells to stress signals is critical for the integrity of the feto-maternal interface and, by extension, survival of the conceptus. O-GlcNAcylation is an essential post-translational modification that links glucose sensing to cellular stress resistance. Unexpectedly, decidualization of primary endometrial stromal cells (EnSCs) was associated with a 60% reduction in O-GlcNAc modified proteins, reflecting downregulation of the enzyme that adds O-GlcNAc to substrates (O-GlcNAc transferase, OGT) but not the enzyme that removes the modification (O-GlcNAcase, OGA)...
December 13, 2017: Endocrinology
https://www.readbyqxmd.com/read/29237092/artificial-cysteine-s-glycosylation-induced-by-per-o-acetylated-unnatural-monosacharides-during-metabolic-glycan-labeling
#14
Wei Qin, Ke Qin, Xinqi Fan, Linghang Peng, Weiyao Hong, Yuntao Zhu, Pinou Lv, Yifei Du, Rongbing Huang, Mengting Han, Bo Cheng, Yuan Liu, Wen Zhou, Chu Wang, Xing Chen
Here we report an unexpected, non-enzymatic cysteine S-glycosylation induced by per-O-acetylated monosaccharides and their clickable analogs on various proteins. This artificial S-glycosylation broadly compromises the specificity and validity of metabolic glycan labeling in living cells using per-O-acetylated azido and alkynyl sugars, which has been overlooked in the field for decades. We demonstrate that free unnatural sugars can avoid the artifacts and by using N-azidoactylgalactosamine, we provide a corrected list of O-GlcNAcylated proteins and O-GlcNAc sites in HeLa cells...
December 13, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/29223644/functional-significance-of-o-glcnac-modification-in-regulating-neuronal-properties
#15
REVIEW
Hongik Hwang, Hyewhon Rhim
Post-translational modifications (PTMs) covalently modify proteins and diversify protein functions. Along with protein phosphorylation, another common PTM is the addition of O-linked β-N-acetylglucosamine (O-GlcNAc) to serine and/or threonine residues. O-GlcNAc modification is similar to phosphorylation in that it occurs to serine and threonine residues and cycles on and off with a similar time scale. However, a striking difference is that the addition and removal of the O-GlcNAc moiety on all substrates are mediated by the two enzymes regardless of proteins, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively...
December 6, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29208956/pol%C3%AE-o-glcnacylation-governs-genome-integrity-during-translesion-dna-synthesis
#16
Xiaolu Ma, Hongmei Liu, Jing Li, Yihao Wang, Yue-He Ding, Hongyan Shen, Yeran Yang, Chenyi Sun, Min Huang, Yingfeng Tu, Yang Liu, Yongliang Zhao, Meng-Qiu Dong, Ping Xu, Tie-Shan Tang, Caixia Guo
DNA polymerase η (Polη) facilitates translesion DNA synthesis (TLS) across ultraviolet (UV) irradiation- and cisplatin-induced DNA lesions implicated in skin carcinogenesis and chemoresistant phenotype formation, respectively. However, whether post-translational modifications of Polη are involved in these processes remains largely unknown. Here, we reported that human Polη undergoes O-GlcNAcylation at threonine 457 by O-GlcNAc transferase upon DNA damage. Abrogation of this modification results in a reduced level of CRL4CDT2-dependent Polη polyubiquitination at lysine 462, a delayed p97-dependent removal of Polη from replication forks, and significantly enhanced UV-induced mutagenesis even though Polη focus formation and its efficacy to bypass across cyclobutane pyrimidine dimers after UV irradiation are not affected...
December 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/29204729/-nutrient-sensing-and-self-renewal-o-glcnac-in-a-new-role
#17
REVIEW
Nikita S Sharma, Ashok K Saluja, Sulagna Banerjee
Whether embryonic, hematopoietic or cancer stem cells, this metabolic reprogramming is dependent on the nutrient-status and bioenergetic pathways that is influenced by the micro-environmental niches like hypoxia. Thus, the microenvironment plays a vital role in determining the stem cell fate by inducing metabolic reprogramming. Under the influence of the microenvironment, like hypoxia, the stem cells have increased glucose and glutamine uptake which result in activation of hexosamine biosynthesis pathway (HBP) and increased O-GlcNAc Transferase (OGT)...
December 5, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/29196265/elevated-o-glcnacylation-stabilizes-foxm1-by-its-reduced-degradation-via-gsk-3%C3%AE-inactivation-in-a-human-gastric-carcinoma-cell-line-mkn45%C3%A2-cells
#18
Yosuke Inoue, Kazumasa Moriwaki, Yasuhiro Ueda, Toshihisa Takeuchi, Kazuhide Higuchi, Michio Asahi
O-GlcNAcylation is a dynamic post-translational modification of cytonuclear proteins for intracellular signaling. Elevated O-GlcNAcylation is a general feature of cancer and contributes to cancer progression, and recent studies indicate the contribution to increasing incidence of various types of cancer in diabetic patients. However, the role of O-GlcNAcylation in tumor progression is not fully elucidated. Forkhead box M1 (FOXM1), a master mitotic transcription factor, has been implicated in all major hallmarks of cancer, and is wildly expressed in solid tumors...
November 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29187734/o-glcnacylation-is-required-for-b-cell-homeostasis-and-antibody-responses
#19
Jung-Lin Wu, Ming-Feng Chiang, Pan-Hung Hsu, Dong-Yen Tsai, Kuo-Hsuan Hung, Ying-Hsiu Wang, Takashi Angata, Kuo-I Lin
O-linked N-acetylglucosamine (O-GlcNAc) transferase (Ogt) catalyzes O-GlcNAc modification. O-GlcNAcylation is increased after cross-linking of the B-cell receptor (BCR), but the physiological function of this reaction is unknown. Here we show that lack of Ogt in B-cell development not only causes severe defects in the activation of BCR signaling, but also perturbs B-cell homeostasis by enhancing apoptosis of mature B cells, partly as a result of impaired response to B-cell activating factor. O-GlcNAcylation of Lyn at serine 19 is crucial for efficient Lyn activation and Syk interaction in BCR-mediated B-cell activation and expansion...
November 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/29187233/identification-of-o-glcnacylated-proteins-in-plasmodium-falciparum
#20
Mattis Kupferschmid, Moyira Osny Aquino-Gil, Hosam Shams-Eldin, Jörg Schmidt, Nao Yamakawa, Frédéric Krzewinski, Ralph T Schwarz, Tony Lefebvre
BACKGROUND: Post-translational modifications (PTMs) constitute a huge group of chemical modifications increasing the complexity of the proteomes of living beings. PTMs have been discussed as potential anti-malarial drug targets due to their involvement in many cell processes. O-GlcNAcylation is a widespread PTM found in different organisms including Plasmodium falciparum. The aim of this study was to identify O-GlcNAcylated proteins of P. falciparum, to learn more about the modification process and to understand its eventual functions in the Apicomplexans...
November 29, 2017: Malaria Journal
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