Cross Talk Between O-GlcNAcylation and Phosphorylation: Roles in Signaling, Transcription, and Chronic Disease

By Gerald W. Hart, Chad Slawson, G. Ramirez-Correa, Olof Lagerlof. Annual Review of Biochemistry, 2011

1,267 citations recorded by the source corpus.

O-GlcNAcylation is the addition of β-D-N-acetylglucosamine to serine or threonine residues of nuclear and cytoplasmic proteins. O-linked N-acetylglucosamine (O-GlcNAc) was not discovered until the early 1980s and still remains difficult to detect and quantify. Nonetheless, O-GlcNAc is highly abundant and cycles on proteins with a timescale similar to protein phosphorylation. O-GlcNAc occurs in organisms ranging from some bacteria to protozoans and metazoans, including plants and nematodes up the evolutionary tree to man. O-GlcNAcylation is mostly on nuclear proteins, but it occurs in all intracellular compartments, including mitochondria. Recent glycomic analyses have shown that O-GlcNAcylation has surprisingly extensive cross talk with phosphorylation, where it serves as a nutrient/stress sensor to modulate signaling, transcription, and cytoskeletal functions. Abnormal amounts of O-GlcNAcylation underlie the etiology of insulin resistance and glucose toxicity in diabetes, and this type of modification plays a direct role in neurodegenerative disease. Many oncogenic proteins and tumor suppressor proteins are also regulated by O-GlcNAcylation. Current data justify extensive efforts toward a better understanding of this invisible, yet abundant, modification. As tools for the study of O-GlcNAc become more facile and available, exponential growth in this area of research will eventually take place.

Subfields: Immunology, Molecular Biology, Organic Chemistry

View Paper: https://www.semanticscholar.org/paper/9958969ec5b7b29335d84f18ced33080c20e058a

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In Immunology

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Citations in the corpus

• Metabolic reprogramming and epigenetic modifications on the path to cancer (2021, background): “This PTM modulation of BCAT2 promotes its degradation and suppresses BCAA catabolism and pancreatic cancer progression (Lei et al., 2020).”
• Protein Glycosylation in Cancer (2015, background): “A fascinating modification of intracellular cytoplasmic, nuclear, and mitochondrial proteins was discovered in 1984: the enzymatic addition of a single sugar GlcNAc (O-β-GlcNAc) donated by UDP-GlcNAc to specific Ser/Thr residues of proteins by the enzyme O-GlcNAc transferase (OGT) (48).”