OGT: a short overview of an enzyme standing out from usual glycosyltransferases

2017 ◽  
Vol 45 (2) ◽  
pp. 365-370 ◽  
Author(s):  
Moyira Aquino-Gil ◽  
Annick Pierce ◽  
Yobana Perez-Cervera ◽  
Edgar Zenteno ◽  
Tony Lefebvre
Keyword(s):  
Glycoside Hydrolase ◽  
Biological Systems ◽  
Nutrient Status ◽  
Post Translational Modification ◽  
Master Regulator ◽  
Short Overview ◽  
Cell Life ◽  
Living Organisms ◽  
Glcnac Transferase

O-GlcNAcylation is a highly dynamic post-translational modification whose level depends on nutrient status. Only two enzymes regulate O-GlcNAcylation cycling, the glycosyltransferase OGT (O-GlcNAc transferase) and the glycoside hydrolase OGA (O-GlcNAcase), that add and remove the GlcNAc moiety to and from acceptor proteins, respectively. During the last 30 years, OGT has emerged as a master regulator of cell life with O-GlcNAcylation being found in viruses, bacteria, insects, protists and metazoans. The study of OGT in different biological systems opens new perspectives for understanding this enzyme in many kingdoms of life. In this review, we summarize recent and older findings regarding the distribution of OGT in living organisms.

O-GlcNAc transferase inhibitors: current tools and future challenges

2016 ◽  
Vol 44 (1) ◽  
pp. 88-93 ◽  
Author(s):  
Riccardo Trapannone ◽  
Karim Rafie ◽  
Daan M.F. van Aalten
Keyword(s):  
Animal Models ◽  
Biological Systems ◽  
Biological Role ◽  
Present Review ◽  
Biological Functions ◽  
Post Translational Modification ◽  
Embryonic Lethal ◽  
Future Challenges ◽  
Glcnac Transferase

The O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification (O-GlcNAcylation) is the dynamic and reversible attachment of N-acetylglucosamine to serine and threonine residues of nucleocytoplasmic target proteins. It is abundant in metazoa, involving hundreds of proteins linked to a plethora of biological functions with implications in human diseases. The process is catalysed by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) that add and remove sugar moieties respectively. OGT knockout is embryonic lethal in a range of animal models, hampering the study of the biological role of O-GlcNAc and the dissection of catalytic compared with non-catalytic roles of OGT. Therefore, selective and potent chemical tools are necessary to inhibit OGT activity in the context of biological systems. The present review focuses on the available OGT inhibitors and summarizes advantages, limitations and future challenges.

scholarly journals Feedback Regulation of O-GlcNAc Transferase through Translation Control to Maintain Intracellular O-GlcNAc Homeostasis

2021 ◽  
Vol 22 (7) ◽  
pp. 3463
Author(s):  
Chia-Hung Lin ◽  
Chen-Chung Liao ◽  
Mei-Yu Chen ◽  
Teh-Ying Chou
Keyword(s):  
Molecular Mechanisms ◽  
Mrna Level ◽  
Feedback Regulation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Cell Physiology ◽  
Hydroxyl Groups ◽  
Post Translational Modification ◽  
Translation Control ◽  
Glcnac Transferase

Protein O-GlcNAcylation is a dynamic post-translational modification involving the attachment of N-acetylglucosamine (GlcNAc) to the hydroxyl groups of Ser/Thr residues on numerous nucleocytoplasmic proteins. Two enzymes are responsible for O-GlcNAc cycling on substrate proteins: O-GlcNAc transferase (OGT) catalyzes the addition while O-GlcNAcase (OGA) helps the removal of GlcNAc. O-GlcNAcylation modifies protein functions; therefore, dysregulation of O-GlcNAcylation affects cell physiology and contributes to pathogenesis. To maintain homeostasis of cellular O-GlcNAcylation, there exists feedback regulation of OGT and OGA expression responding to fluctuations of O-GlcNAc levels; yet, little is known about the molecular mechanisms involved. In this study, we investigated the O-GlcNAc-feedback regulation of OGT and OGA expression in lung cancer cells. Results suggest that, upon alterations in O-GlcNAcylation, the regulation of OGA expression occurs at the mRNA level and likely involves epigenetic mechanisms, while modulation of OGT expression is through translation control. Further analyses revealed that the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) contributes to the downregulation of OGT induced by hyper-O-GlcNAcylation; the S5A/S6A O-GlcNAcylation-site mutant of 4E-BP1 cannot support this regulation, suggesting an important role of O-GlcNAcylation. The results provide additional insight into the molecular mechanisms through which cells may fine-tune intracellular O-GlcNAc levels to maintain homeostasis.

Biopolymers: A comprehensive review

2022 ◽  
Vol 4 (1) ◽  
pp. 013-018
Author(s):  
Mohini Chandrashekhar Upadhye ◽  
Mohini Chetan Kuchekar ◽  
Rohini Revansiddhappa Pujari ◽  
Nutan Uttam Sable
Keyword(s):  
Pharmaceutical Industry ◽  
Food Packaging ◽  
Biological Systems ◽  
Review Article ◽  
Skin Care ◽  
Comprehensive Review ◽  
Green Nanotechnology ◽  
Biological Sources ◽  
Living Organisms

Biopolymers are compounds prepared by using various living organisms, including plants. These are composed of repeated units of the same or similar structure (monomers) linked together. Rubber, starch, cellulose, proteins and DNA, RNA, chitin, and peptides are some of the examples of natural biopolymers. Biopolymers are a diverse and remarkably versatile class of materials that are either produced by biological systems or synthesize from biological sources. Biopolymers are used in pharmaceutical industry and also in food industry.Naturally derived polymers are also used for conditioning benefits in hair and skin care. Biopolymers have various applications in medicine, food, packaging, and petroleum industries. This review article is focused on various aspects of biopolymers with a special emphasis on role of biopolymers in green nanotechnology and agriculture.

scholarly journals Use of biophysical methods to improve yields and quality of agricultural products

2008 ◽  
Vol 53 (3) ◽  
pp. 235-242 ◽  
Author(s):  
Branko Marinkovic ◽  
Miroslav Grujic ◽  
Dusko Marinkovic ◽  
Jovan Crnobarac ◽  
Jelena Marinkovic ◽  
...  
Keyword(s):  
Radiation Effects ◽  
Biological Systems ◽  
Low Frequency ◽  
Crop Species ◽  
Human Environment ◽  
Electromagnetic Stimulation ◽  
Stimulation Method ◽  
Living Organisms ◽  
Novi Sad ◽  
The University

Until as recently as a century ago, the exposure of biological systems to radiation was limited only to the natural sources. Today, however, a broad range of radiation types and doses have found a wide variety of uses and applications, so much so that it would be difficult to make a list of all the areas of human activity in which radiation is used for one purpose or another. The study of radiation effects on individuals and populations as a whole has become important only with the development of methods and sources of man-made radiation. Given that what is present in this case are physical effects on biological systems (living organisms), all these methods can be placed under the heading of biophysical influences. In the last 50 years, the effects of extremely low-frequency electromagnetic fields (ELF-EMF) have been studied with great diligence. These fields are the ones most commonly found in the human environment and they have been used in our studies in this field. The present paper provides a brief review of the literature data and our findings on the effects of ELF-EMF on various crop species using the RIES (Resonant Impulse Electromagnetic Stimulation) method, developed at the Faculty of Agriculture of the University of Novi Sad.

The sweet side of AMPK signaling: regulation of GFAT1

2017 ◽  
Vol 474 (7) ◽  
pp. 1289-1292 ◽  
Author(s):  
John W. Scott ◽  
Jonathan S. Oakhill
Keyword(s):  
Energy Demand ◽  
Dynamic Control ◽  
Cellular Protein ◽  
Post Translational Modification ◽  
Nutrient Metabolism ◽  
Ampk Signaling ◽  
Biochemical Journal ◽  
Signaling Axis ◽  
Hexosamine Biosynthesis ◽  
Living Organisms

Maintaining a steady balance between nutrient supply and energy demand is essential for all living organisms and is achieved through the dynamic control of metabolic processes that produce and consume adenosine-5′-triphosphate (ATP), the universal currency of energy in all cells. A key sensor of cellular energy is the adenosine-5′-monophosphate (AMP)-activated protein kinase (AMPK), which is the core component of a signaling network that regulates energy and nutrient metabolism. AMPK is activated by metabolic stresses that decrease cellular ATP, and functions to restore energy balance by orchestrating a switch in metabolism away from anabolic pathways toward energy-generating catabolic processes. A new study published in a recent issue of Biochemical Journal by Zibrova et al. shows that glutamine:fructose-6-phosphate amidotransferase-1 (GFAT1), the rate-limiting enzyme of the hexosamine biosynthesis pathway (HBP), is a physiological substrate of AMPK. The HBP is an offshoot of the glycolytic pathway that drives the synthesis of uridine-5′-diphospho-N-acetylglucosamine, the requisite donor metabolite needed for dynamic β-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) of cellular proteins. O-GlcNAcylation is a nutrient-sensitive post-translational modification that, like phosphorylation, regulates numerous intracellular processes. Zibrova et al. show that inhibitory phosphorylation of the GFAT1 residue Ser243 by AMPK in response to physiological or small-molecule activators leads to a reduction in cellular protein O-GlcNAcylation. Further work revealed that AMPK-dependent phosphorylation of GFAT1 promotes angiogenesis in endothelial cells. This elegant study demonstrates that the AMPK–GFAT1 signaling axis serves as an important communication point between two nutrient-sensitive signaling pathways and is likely to play a significant role in controlling physiological processes in many other tissues.

Biotechnology

2021 ◽  
pp. 112-132
Author(s):  
Qing-Ping Ma
Keyword(s):  
Gene Therapy ◽  
Energy Consumption ◽  
Biological Systems ◽  
Hereditary Diseases ◽  
Future Trends ◽  
Current State ◽  
Ore Processing ◽  
Living Organisms ◽  
High Yields ◽  
Reducing Energy

Biotechnology utilizes biological systems or living organisms to create, develop, or make products. This chapter reviews the current state of biotechnology and examines its future trends. Currently, biotechnology plays key roles in medicine, agriculture, and industry. In medicine, vaccines which still rely on biological systems for their production, are the best tools to prevent infectious diseases; antibodies and RNA/DNA probes have been crucial in detecting and treating diseases; and genetic editing and gene therapy is making it possible to treat hereditary diseases. In agriculture, biotechnology is generating crops that produce high yields and need fewer inputs, crops that need fewer applications of pesticides, and crops with enhanced nutrition profiles. In industry, biotechnology is being utilized in food processing, metal ore processing, the production of chemicals, and reducing energy consumption and pollution.

scholarly journals O-GlcNAc regulates gene expression by controlling detained intron splicing

2020 ◽  
Vol 48 (10) ◽  
pp. 5656-5669 ◽  
Author(s):  
Zhi-Wei Tan ◽  
George Fei ◽  
Joao A Paulo ◽  
Stanislav Bellaousov ◽  
Sara E S Martin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Intron Splicing ◽  
Post Translational Modification ◽  
Substantial Fraction ◽  
Control Gene Expression ◽  
Almost All ◽  
Glcnac Transferase ◽  
Eukaryotic Genomes ◽  
Specific Inhibitors ◽  
Nutrient Conditions

Abstract Intron detention in precursor RNAs serves to regulate expression of a substantial fraction of genes in eukaryotic genomes. How detained intron (DI) splicing is controlled is poorly understood. Here, we show that a ubiquitous post-translational modification called O-GlcNAc, which is thought to integrate signaling pathways as nutrient conditions fluctuate, controls detained intron splicing. Using specific inhibitors of the enzyme that installs O-GlcNAc (O-GlcNAc transferase, or OGT) and the enzyme that removes O-GlcNAc (O-GlcNAcase, or OGA), we first show that O-GlcNAc regulates splicing of the highly conserved detained introns in OGT and OGA to control mRNA abundance in order to buffer O-GlcNAc changes. We show that OGT and OGA represent two distinct paradigms for how DI splicing can control gene expression. We also show that when DI splicing of the O-GlcNAc-cycling genes fails to restore O-GlcNAc homeostasis, there is a global change in detained intron levels. Strikingly, almost all detained introns are spliced more efficiently when O-GlcNAc levels are low, yet other alternative splicing pathways change minimally. Our results demonstrate that O-GlcNAc controls detained intron splicing to tune system-wide gene expression, providing a means to couple nutrient conditions to the cell's transcriptional regime.

5. Robots and artificial life

2018 ◽  
Author(s):  
Margaret A. Boden
Keyword(s):  
Artificial Life ◽  
Biological Systems ◽  
Evolutionary Programming ◽  
Self Organization ◽  
Big Business ◽  
Practical Applications ◽  
Living Organisms ◽  
Self Organizing

Artificial life (A-Life) models biological systems. Like AI, it has both technological and scientific aims. ‘Robots and artificial life’ explains that A-Life is integral to AI, because all the intelligence we know about is found in living organisms. AI technologists turn to biology in developing practical applications of many kinds, including robots, evolutionary programming, and self-organizing devices. Robots are quintessential examples of AI, having high visibility and being hugely ingenious—and very big business, too. Evolutionary AI, although widely used, is less well known. Self-organizing machines are even less familiar. Nevertheless, in the quest to understand self-organization, AI has been as useful to biology as biology has been to AI.

scholarly journals Enzymes of yeast polyphosphate metabolism: structure, enzymology and biological roles

2016 ◽  
Vol 44 (1) ◽  
pp. 234-239 ◽  
Author(s):  
Rūta Gerasimaitė ◽  
Andreas Mayer
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Blood Coagulation ◽  
Bone Mineralization ◽  
Inorganic Polyphosphate ◽  
Yeast Saccharomyces Cerevisiae ◽  
Future Directions ◽  
Short Overview ◽  
Metabolism Enzymes ◽  
Living Organisms ◽  
Polyphosphate Metabolism

Inorganic polyphosphate (polyP) is found in all living organisms. The known polyP functions in eukaryotes range from osmoregulation and virulence in parasitic protozoa to modulating blood coagulation, inflammation, bone mineralization and cellular signalling in mammals. However mechanisms of regulation and even the identity of involved proteins in many cases remain obscure. Most of the insights obtained so far stem from studies in the yeast Saccharomyces cerevisiae. Here, we provide a short overview of the properties and functions of known yeast polyP metabolism enzymes and discuss future directions for polyP research.

scholarly journals Recognition of a glycosylation substrate by the O-GlcNAc transferase TPR repeats

Open Biology ◽  
2017 ◽  
Vol 7 (6) ◽  
pp. 170078 ◽  
Author(s):  
Karim Rafie ◽  
Olawale Raimi ◽  
Andrew T. Ferenbach ◽  
Vladimir S. Borodkin ◽  
Vaibhav Kapuria ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Substrate Specificity ◽  
Active Site ◽  
Target Site ◽  
Post Translational Modification ◽  
Tetratricopeptide Repeats ◽  
Protein Substrates ◽  
Nucleocytoplasmic Proteins ◽  
Glcnac Transferase ◽  
Single Enzyme

O-linked N -acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. Although a single enzyme, O-GlcNAc transferase (OGT), generates the entire cytosolic O-GlcNAc proteome, it is not understood how it recognizes its protein substrates, targeting only a fraction of serines/threonines in the metazoan proteome for glycosylation. We describe a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein, revealing extensive interactions with the tetratricopeptide repeats of OGT. Confirmed by mutagenesis, this interaction suggests that glycosylation substrate specificity is achieved by recognition of a degenerate sequon in the active site combined with an extended conformation C-terminal of the O-GlcNAc target site.

Sign in / Sign up

Export Citation Format

Share Document