Oglcnacylation

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Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. This protein modification interacts with key cellular pathways involved in transcription, translation, and proteostasis. Although ubiquitous throughout the body, O-GlcNAc is particularly abundant in the brain, and various proteins commonly found at synapses are O-GlcNAcylated.

Oglcnacylation

Federal government websites often end in. The site is secure. O -linked N -acetylglucosamine O -GlcNAc is a dynamic post-translational modification occurring on myriad proteins in the cell nucleus, cytoplasm, and mitochondria. O -GlcNAcylation is involved in a number of important cell processes including transcription, translation, metabolism, signal transduction, and apoptosis. Deregulation of O -GlcNAcylation has been reported to be associated with various human diseases such as cancer, diabetes, neurodegenerative diseases, and cardiovascular diseases. A better understanding of the roles of O -GlcNAcylation in physiopathological processes would help to uncover novel avenues for therapeutic intervention. The aim of this review is to discuss the recent updates on the mechanisms and impacts of O -GlcNAcylation on these diseases, and its potential as a new clinical target. Later studies demonstrated that, differing from traditional forms of protein glycosylation, which are stable and mostly restricted to endoplasmic reticulum and Golgi resident, O -GlcNAcylation is a dynamic and reversible modification, and mainly occurs in the cytoplasm, mitochondria, and nucleus Issad et al. Moreover, O -GlcNAcylation has been shown to have extensive interplay with phosphorylation through regulating the phosphorylation of adjacent residues or competing for the same serine or threonine residue Leney et al. Glutamine-fructosephosphate amidotransferase GFAT , which converts fructosephosphate to glucosaminephosphate, is the first and rate-limiting enzyme of HBP Teo et al. All OGT isoforms contain two distinct domains: an N-terminal domain containing tetraticopeptide repeat TPR motifs which are important for the recognition of different protein substrates, and a C-terminal domain that possesses glycosyltransferase activity Liu et al. OGA, the single enzyme responsible for removing O -GlcNAc, contains two domains—a hexosaminidase domain at the N-terminal and a histone acetyltransferase domain at the C-terminal of the protein.

In the meantime, to ensure oglcnacylation support, we are displaying the site without styles and JavaScript. O-GlcNAc modification protects against protein misfolding and aggregation in neurodegenerative disease, oglcnacylation. Genes Dev 18 18 —

Journal of Biomedical Science volume 27 , Article number: 57 Cite this article. Metrics details. O -GlcNAcylation couples the processes of nutrient sensing, metabolism, signal transduction and transcription, and plays important roles in development, normal physiology and physiopathology. Particularly, O -GlcNAcylation has been shown to have intricate crosstalk with phosphorylation as they both modify serine or threonine residues. Aberrant O -GlcNAcylation on various protein substrates has been implicated in many diseases, including neurodegenerative diseases, diabetes and cancers.

Molecular Medicine volume 28 , Article number: Cite this article. Metrics details. In eukaryotes, only two conserved enzymes are involved in this process. Aberrant O -GlcNAcylation is associated with a variety of human diseases, such as diabetes, cancer, neurodegenerative diseases, and cardiovascular diseases. Numerous studies have confirmed that O -GlcNAcylation is involved in the occurrence and progression of cancers in multiple systems throughout the body. It is also involved in regulating multiple cancer hallmarks, such as metabolic reprogramming, proliferation, invasion, metastasis, and angiogenesis.

Oglcnacylation

Metrics details. Histones display a wide variety of post-translational modifications, including acetylation, methylation, and phosphorylation. These epigenetic modifications can influence chromatin structure and function without altering the DNA sequence. Histones can also undergo post-translational O- GlcNAcylation, a rather understudied modification that plays critical roles in almost all biological processes and is added and removed by O- linked N- acetylglucosamine transferase and O- GlcNAcase, respectively.

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Cell 55 , — Davie, C. What is type 2 diabetes? Cellular O -GlcNAcylation levels may be maintained within an 'optimal zone' by a 'buffering system' that is generated by mutual regulation of OGT and OGA at the transcriptional and post-translational levels. Mutants on the dimerization interface of TPR superhelices prevent the formation of TPR dimers in solution and cause moderate reduction of the enzymatic activity of OGT toward nucleoporin p62 [ 40 ]. Article Google Scholar. You can also search for this author in PubMed Google Scholar. Mitochondrial and nucleocytoplasmic isoforms of O-linked GlcNAc transferase encoded by a single mammalian gene. Issue Date : July Reduced O glycosylation of Sp1 is associated with increased proteasome susceptibility. For OGT, studies have shown that substrate recognition is regulated by a number of factors including aspartate [19] and asparagine [20] ladder motifs in the lumen of the superhelical TPR domain, active site residues, [21] and adaptor proteins. November

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Nat Cell Biol. Dynamic glycosylation of nuclear and cytosolic proteins. Front Immunol. OGA is highly conserved among species [ 47 ]. Although there is one example of substrate binding to the catalytic domain alone 29 , the majority of substrate binding is suggested to occur in the TPR domain of OGT. PowerPoint slides. The O-GlcNAc transferase gene resides on the X chromosome and is essential for embryonic stem cell viability and mouse ontogeny. These results show that O -GlcNAcylation and phosphorylation do not always occur reciprocally. O -GlcNAc has been found to slow protein aggregation, though the generality of this phenomenon is unknown. PD patients generally develop motor symptoms, including rigidity, bradykinesia, and postural instability 95 , 96 , 97 , Swamy, M. OGA inhibitors have recently entered early clinical trials for the treatment of Progressive Supranuclear Palsy [ ] as O -GlcNAcylation of Tau blocks the pathological effects of phosphorylation and aggregation of Tau [ 76 ]. Fulop, N. Lazarus, B. Synergy of peptide and sugar in O -GlcNAcase substrate recognition.