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Cited by 63Glycosylation and Glycoproteins ResearchCarbohydrate Chemistry and SynthesisRedox biology and oxidative stress

The Beginner’s Guide to O-GlcNAc: From Nutrient Sensitive Pathway Regulation to Its Impact on the Immune System

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Mannino, Michael P., Hart, Gerald W.·2022·Frontiers in Immunology
DOI 10.3389/fimmu.2022.828648PMC PMC8841346
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Abstract

The addition of N-acetyl glucosamine (GlcNAc) on the hydroxy group of serine/threonine residues is known as O-GlcNAcylation (OGN). The dynamic cycling of this monosaccharide on and off substrates occurs via O-linked β-N-acetylglucosamine transferase (OGT) and O-linked β-N-acetylglucosaminase (OGA) respectively. These enzymes are found ubiquitously in eukaryotes and genetic knock outs of the ogt gene has been found to be lethal in embryonic mice. The substrate scope of these enzymes is vast, over 15,000 proteins across 43 species have been identified with O-GlcNAc. OGN has been known to play a key role in several cellular processes such as: transcription, translation, cell signaling, nutrient sensing, immune cell development and various steps of the cell cycle. However, its dysregulation is present in various diseases: cancer, neurodegenerative diseases, diabetes.O-GlcNAc is heavily involved in cross talk with other post-translational modifications (PTM), such as phosphorylation, acetylation, and ubiquitination, by regulating each other’s cycling enzymes or directly competing addition on the same substrate. This crosstalk between PTMs can affect gene expression, protein localization, and protein stability; therefore, regulating a multitude of cell signaling pathways. In this review the roles of OGN will be discussed. The effect O-GlcNAc exerts over protein-protein interactions, the various forms of crosstalk with other PTMs, and its role as a nutrient sensor will be highlighted. A summary of how these O-GlcNAc driven processes effect the immune system will also be included.

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Cited by

Sorted by citations

Authors
Mannino, M. P., & Hart, G. W.
Affiliations
University of Georgia (US)
Corresponding author
Hart, Gerald W.
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2022-01-31
Volume
13
Pages
828648-828648
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2022.828648
PMC
PMC8841346
OpenAlex
W4210450221
Cited by
63
References
3
Citations by year
2026: 15 · 2025: 13 · 2024: 18 · 2023: 13 · 2022: 4
FWCI
1.26
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institutes of Health
  • National Institute of General Medical Sciences (R01GM116891)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
  • Physical Sciences › Chemistry › Organic Chemistry › Carbohydrate Chemistry and Synthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
O-GlcNAc, O-GlcNAc transferase, O-GlcNAcase, nutrient sensing, post-translational modification crosstalk, immune cell development, protein-protein interaction, protein stability, signal transduction
MeSH terms
Acetylglucosamine, Animals, Humans, Immune System, Lymphocyte Activation, Phosphorylation, Protein Processing, Post-Translational, Signal Transduction, N-Acetylglucosaminyltransferases, Ubiquitination

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