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

Annu Rev Biochem. 2011;80:825-58. doi: 10.1146/annurev-biochem-060608-102511.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Acetylglucosamine / chemistry
  • Acetylglucosamine / metabolism*
  • Animals
  • Chronic Disease*
  • Diabetes Mellitus / physiopathology
  • Glycosylation
  • Humans
  • Models, Molecular
  • Molecular Structure
  • N-Acetylglucosaminyltransferases / metabolism
  • Neoplasms / physiopathology
  • Neurodegenerative Diseases / physiopathology
  • Phosphorylation
  • Protein Conformation
  • Signal Transduction / physiology*
  • Transcription, Genetic*

Substances

  • N-Acetylglucosaminyltransferases
  • Acetylglucosamine