Cross talk between O-GlcNAcylation and phosphorylation: roles in signaling, transcription, and chronic disease

GW Hart, C Slawson, G Ramirez-Correa… - Annual review of …, 2011 - annualreviews.org
Annual review of biochemistry, 2011annualreviews.org
O-GlcNAcylation is the addition of β-DN-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 …
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.
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