Oglcnacylation

These enzymes are found ubiquitously in eukaryotes and genetic knock oglcnacylation of the ogt gene has been found to be lethal in embryonic mice. The substrate scope of these enzymes is vast, over 15, proteins across 43 species have been identified with O -GlcNAc, oglcnacylation.

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. The rate-limiting step of the HBP is catalyzed by the GFAT glutamine fructosephosphate amidotransferase , which uses glutamine to convert fructosephosphate into glucosaminephosphate.

Full-length OGT exists as a trimer [ 38 ], oglcnacylation. Lifespan was significantly increased in the gfat-1 gain-of-function mutants, and supplementation with GlcNAc was sufficient to extend the lifespan by alleviating oglcnacylation and improving protein quality control

O -GlcNAc differs from other forms of protein glycosylation : i O -GlcNAc is not elongated or modified to form more complex glycan structures, ii O -GlcNAc is almost exclusively found on nuclear and cytoplasmic proteins rather than membrane proteins and secretory proteins , and iii O -GlcNAc is a highly dynamic modification that turns over more rapidly than the proteins which it modifies. O -GlcNAc is conserved across metazoans. Due to the dynamic nature of O -GlcNAc and its presence on serine and threonine residues, O -GlcNAcylation is similar to protein phosphorylation in some respects. First reported in , this post-translational modification has since been identified on over 5, proteins. In , the Hart lab was probing for terminal GlcNAc residues on the surfaces of thymocytes and lymphocytes. O -GlcNAc is generally a dynamic modification that can be cycled on and off various proteins. Some residues are thought to be constitutively modified by O -GlcNAc.

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. O -GlcNAcylation is a nutrient- and stress-responsive post-translational modification PTM that involves the attachment of O -linked N -acetylglucosamine moieties to Ser and Thr residues of cytoplasmic, nuclear and mitochondrial proteins. Potential mechanisms that enable a single OGT enzyme to recognize hundreds of protein substrates include substrate-specific interactions with the tetratricopeptide repeat TPR domain of OGT and context-dependent recruitment of OGT to its substrates by a hierarchy of conserved adaptor proteins. Furthermore, in response to cellular stress, O -GlcNAcylation may occur nonspecifically in unstructured regions of unfolded proteins in order to block their aggregation and degradation and facilitate their refolding. O -GlcNAcylation is involved in the spatiotemporal regulation of diverse cellular processes, which include transcription, epigenetic modifications and cell signalling dynamics.

Oglcnacylation

This modification impacts protein functionality, influencing stability, protein-protein interactions, and localization. Its interaction with other modifications such as phosphorylation and ubiquitination is becoming increasingly evident. Dysregulation of O-GlcNAcylation is associated with numerous human diseases, including diabetes, nervous system degeneration, and cancers. This review extensively explores the regulatory mechanisms of O-GlcNAcylation, its effects on cellular physiology, and its role in the pathogenesis of diseases. It examines the implications of aberrant O-GlcNAcylation in diabetes and tumorigenesis, highlighting novel insights into its potential role in cardiovascular diseases. The review also discusses the interplay of O-GlcNAcylation with other protein modifications and its impact on cell growth and metabolism. By synthesizing current research, this review elucidates the multifaceted roles of O-GlcNAcylation, providing a comprehensive reference for future studies. It underscores the potential of targeting the O-GlcNAcylation cycle in developing novel therapeutic strategies for various pathologies.

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Drug Discovery Today. As a result, p53 accumulates in the cytoplasm, allowing for increased apoptotic activity Figure 1 As a library, NLM provides access to scientific literature. Skip to main content Thank you for visiting nature. Some residues are thought to be constitutively modified by O -GlcNAc. Chen, Q. Nevertheless, the significant roles of O -GlcNAcylation in various lineages of immune cells in the physiological state may shed light on the development of new strategies to boost or rejuvenate immune responses against diseases, such as infection or cancer. The addition or removal of O -GlcNAc can alter a variety of biological activities. Int J Mol Sci. Martin, J. Cardioprotection by N -acetylglucosamine linkage to cellular proteins.

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Learn more. Han, C. Zhu-Mauldin, X. View author publications. Wheat germ agglutinin , a plant lectin , is able to recognize terminal GlcNAc residues and is thus often used for detection of O -GlcNAc. Cell , 69—80 To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. Cytosolic O-glycosylation is abundant in nerve terminals. Nuclear pore complex glycoproteins contain cytoplasmically disposed O-linked N-acetylglucosamine. Blocking O -linked GlcNAc cycling in Drosophila insulin-producing cells perturbs glucose-insulin homeostasis. Nat Chem Biol 13 6 —2. J Cereb Blood Flow Metab.