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.

Diversity of the SUMOylation machinery in plants

2010 ◽  
Vol 38 (1) ◽  
pp. 60-64 ◽  
Author(s):  
L. Maria Lois
Keyword(s):  
Current Knowledge ◽  
Biological Role ◽  
Present Review ◽  
Post Translational Modification ◽  
Biochemical Studies ◽  
High Degree

In the last decade, SUMOylation has emerged as an essential post-translational modification in eukaryotes. In plants, the biological role of SUMO (small ubiquitin-related modifier) has been studied through genetic approaches that together with recent biochemical studies suggest that the plant SUMOylation system has a high degree of complexity. The present review summarizes our current knowledge on the SUMOylation system in Arabidopsis, focusing on the mechanistic properties of the machinery components identified.

Insights into biological functions across species: examining the role of Rab proteins in YIP1 family function

2005 ◽  
Vol 33 (4) ◽  
pp. 614-618 ◽  
Author(s):  
C.Z. Chen ◽  
R.N. Collins
Keyword(s):  
Membrane Proteins ◽  
Protein Function ◽  
Evolutionary Conservation ◽  
Biological Role ◽  
Rab Proteins ◽  
Biological Functions ◽  
Human Homologue ◽  
Family Function ◽  
Evolutionarily Conserved

The YIP1 family comprises an evolutionarily conserved group of membrane proteins, which share the ability to bind di-prenylated Rab proteins. The biochemical capability of YIP1 family proteins suggests a possible role in the cycle of physical localization of Rab proteins between their cognate membranes and the cytosol. YIP1 is essential for viability in yeast and a deletion of YIP1 can be rescued with the human homologue YIP1A. We have made use of this evolutionary conservation of function to generate a series of mutant alleles of YIP1 to investigate the biological role of Yip1p. Our findings indicate evidence for the participation of Yip1p in both Rab and COPII protein function; at present, we are not able to distinguish between the models that these roles represent, i.e. independent or dependent activities of Yip1p.

Biological role of glutathione in nitric oxide-induced toxicity in cell culture and animal models

2005 ◽  
Vol 39 (11) ◽  
pp. 1489-1498 ◽  
Author(s):  
C LI ◽  
T WRIGHT ◽  
M DONG ◽  
Y DOMMELS ◽  
L TRUDEL ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Culture ◽  
Animal Models ◽  
Biological Role

scholarly journals Chemical approaches for profiling dynamic palmitoylation

2013 ◽  
Vol 41 (1) ◽  
pp. 43-49 ◽  
Author(s):  
Brent R. Martin
Keyword(s):  
Global Analysis ◽  
Present Review ◽  
Post Translational Modification ◽  
Enzymatic Regulation ◽  
Protein Palmitoylation ◽  
Future Challenges ◽  
Selective Chemical ◽  
Cellular Pathways ◽  
Membrane Compartmentalization ◽  
The Impact

Protein palmitoylation is a critical post-translational modification important for membrane compartmentalization, trafficking and regulation of many key signalling proteins. Recent non-radioactive chemo-proteomic labelling methods have enabled a new focus on this emerging regulatory modification. Palmitoylated proteins can now be profiled in complex biological systems by MS for direct annotation and quantification. Based on these analyses, palmitoylation is clearly widespread and broadly influences the function of many cellular pathways. The recent introduction of selective chemical labelling approaches has opened new opportunities to revisit long-held questions about the enzymatic regulation of this widespread post-translational modification. In the present review, we discuss the impact of new chemical labelling approaches and future challenges for the dynamic global analysis of protein palmitoylation.

scholarly journals MARTs and MARylation in the Cytosol: Biological Functions, Mechanisms of Action, and Therapeutic Potential

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 313
Author(s):  
Sridevi Challa ◽  
MiKayla S. Stokes ◽  
W. Lee Kraus
Keyword(s):  
Stress Responses ◽  
Molecular Mechanisms ◽  
Neuronal Development ◽  
New Technologies ◽  
Therapeutic Potential ◽  
Structural Features ◽  
Cellular Transport ◽  
Biological Functions ◽  
Post Translational Modification

Mono(ADP-ribosyl)ation (MARylation) is a regulatory post-translational modification of proteins that controls their functions through a variety of mechanisms. MARylation is catalyzed by mono(ADP-ribosyl) transferase (MART) enzymes, a subclass of the poly(ADP-ribosyl) polymerase (PARP) family of enzymes. Although the role of PARPs and poly(ADP-ribosyl)ation (PARylation) in cellular pathways, such as DNA repair and transcription, is well studied, the role of MARylation and MARTs (i.e., the PARP ‘monoenzymes’) are not well understood. Moreover, compared to PARPs, the development of MART-targeted therapeutics is in its infancy. Recent studies are beginning to shed light on the structural features, catalytic targets, and biological functions of MARTs. The development of new technologies to study MARTs have uncovered essential roles for these enzymes in the regulation of cellular processes, such as RNA metabolism, cellular transport, focal adhesion, and stress responses. These insights have increased our understanding of the biological functions of MARTs in cancers, neuronal development, and immune responses. Furthermore, several novel inhibitors of MARTs have been developed and are nearing clinical utility. In this review, we summarize the biological functions and molecular mechanisms of MARTs and MARylation, as well as recent advances in technology that have enabled detection and inhibition of their activity. We emphasize PARP-7, which is at the forefront of the MART subfamily with respect to understanding its biological roles and the development of therapeutically useful inhibitors. Collectively, the available studies reveal a growing understanding of the biochemistry, chemical biology, physiology, and pathology of MARTs.

scholarly journals The Role of O-GlcNAcylation in Immune Cell Activation

2021 ◽  
Vol 12 ◽  
Author(s):  
Amy Qiang ◽  
Chad Slawson ◽  
Patrick E. Fields
Keyword(s):  
Cell Activation ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Nutrient Sensing ◽  
Post Translational Modification ◽  
Immune Cell Activation ◽  
Glcnac Transferase ◽  
Diabetes And Obesity ◽  
Normal Cellular Function

O-GlcNAcylation is a dynamic post-translational modification where the sugar, O-linked β-N-acetylglucosamine (O-GlcNAc) is added to or removed from various cytoplasmic, nuclear, and mitochondrial proteins. This modification is regulated by only two enzymes: O-GlcNAc transferase (OGT), which adds O-GlcNAc, and O-GlcNAcase (OGA), which removes the sugar from proteins. O-GlcNAcylation is integral to maintaining normal cellular function, especially in processes such as nutrient sensing, metabolism, transcription, and growth and development of the cell. Aberrant O-GlcNAcylation has been associated with a number of pathological conditions, including, neurodegenerative diseases, cancer, diabetes, and obesity. However, the role of O-GlcNAcylation in immune cell growth/proliferation, or other immune responses, is currently incompletely understood. In this review, we highlight the effects of O-GlcNAcylation on certain cells of the immune system, especially those involved in pro-inflammatory responses associated with diabetes and obesity.

scholarly journals O-GlcNAcase contributes to cognitive function in Drosophila

2020 ◽  
Vol 295 (26) ◽  
pp. 8636-8646
Author(s):  
Villo Muha ◽  
Michaela Fenckova ◽  
Andrew T. Ferenbach ◽  
Marica Catinozzi ◽  
Ilse Eidhof ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Species Loss ◽  
Post Translational Modification ◽  
Axon Terminals ◽  
Hippocampal Synaptic Plasticity ◽  
Evolutionarily Conserved ◽  
Synaptic Boutons ◽  
Larval Neuromuscular Junction ◽  
Glcnac Transferase

O-GlcNAcylation is an abundant post-translational modification in neurons. In mice, an increase in O-GlcNAcylation leads to defects in hippocampal synaptic plasticity and learning. O-GlcNAcylation is established by two opposing enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). To investigate the role of OGA in elementary learning, we generated catalytically inactive and precise knockout Oga alleles (OgaD133N and OgaKO, respectively) in Drosophila melanogaster. Adult OgaD133N and OgaKO flies lacking O-GlcNAcase activity showed locomotor phenotypes. Importantly, both Oga lines exhibited deficits in habituation, an evolutionarily conserved form of learning, highlighting that the requirement for O-GlcNAcase activity for cognitive function is preserved across species. Loss of O-GlcNAcase affected a number of synaptic boutons at the axon terminals of larval neuromuscular junction. Taken together, we report behavioral and neurodevelopmental phenotypes associated with Oga alleles and show that Oga contributes to cognition and synaptic morphology in Drosophila.

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.

scholarly journals The role of oviduct-specific glycoprotein (OVGP1) in modulating biological functions of gametes and embryos

2022 ◽  
Author(s):  
Yuewen Zhao ◽  
Sydney Vanderkooi ◽  
Frederick W. K. Kan
Keyword(s):  
Reproductive Tract ◽  
Mammalian Species ◽  
Early Embryo ◽  
Female Reproductive Tract ◽  
Present Review ◽  
Secretory Cells ◽  
Biological Functions ◽  
Complex Process ◽  
Reproductive Events

AbstractDiverse lines of evidence indicate that the mammalian oviduct makes important contributions to the complex process of reproduction other than being simply a conduit for the transport of gametes and embryos. The cumulative synthesis and transport of proteins secreted by oviductal secretory cells into the oviductal lumen create a microenvironment supporting important reproductive events, including sperm capacitation, fertilization, and early embryo development. Among the components that have been identified in the oviductal fluid is a family of glycosylated proteins known collectively as oviduct-specific glycoprotein (OVGP1) or oviductin. OVGP1 has been identified in several mammalian species, including humans. The present review summarizes the work carried out, in various mammalian species, by many research groups revealing the synthesis and secretion of OVGP1, its fate in the female reproductive tract upon secretion by the oviductal epithelium, and its role in modulating biological functions of gametes and embryos. The production and functions of recombinant human OVGP1 and recombinant OVGP1 of other mammalian species are also discussed. Some of the findings obtained with immunocytochemistry will be highlighted in the present review. It is hoped that the findings obtained from recent studies carried out with recombinant OVGP1 from various species will rekindle researchers’ interest in pursuing further the role of the oviductal microenvironment, of which OVGP1 is a major component, in contributing to the successful occurrence of early reproductive events, and the potential use of OVGP1 in improving the current assisted reproductive technology in alleviating infertility.

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