Cross Talk between O-GlcNAcylation and phosphorylation: Roles in signaling, transcription, and chronic disease

Gerald W. Hart, Chad Slawson, Genaro Ramirez-Correa, Olof Lagerlof

Research output: Contribution to journalArticlepeer-review

Abstract

O-GlcNAcylation is the addition of βÎ2-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.

Original languageEnglish (US)
Pages (from-to)825-858
Number of pages34
JournalAnnual review of biochemistry
Volume80
DOIs
StatePublished - Jul 7 2011

Keywords

  • Alzheimer's disease
  • O-GlcNAc
  • cancer
  • diabetes
  • translation

ASJC Scopus subject areas

  • Biochemistry

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