Modulation of transcription factor function by O-GlcNAc modification

Biochim Biophys Acta. 2010 May-Jun;1799(5-6):353-64. doi: 10.1016/j.bbagrm.2010.02.005. Epub 2010 Mar 2.

Abstract

O-linked beta-N-acetylglucosamine (O-GlcNAc) modification of nuclear and cytoplasmic proteins is important for many cellular processes, and the number of proteins that contain this modification is steadily increasing. This modification is dynamic and reversible, and in some cases competes for phosphorylation of the same residues. O-GlcNAc modification of proteins is regulated by cell cycle, nutrient metabolism, and other extracellular signals. Compared to protein phosphorylation, which is mediated by a large number of kinases, O-GlcNAc modification is catalyzed only by one enzyme called O-linked N-acetylglucosaminyl transferase or OGT. Removal of O-GlcNAc from proteins is catalyzed by the enzyme beta-N-acetylglucosaminidase (O-GlcNAcase or OGA). Altered O-linked GlcNAc modification levels contribute to the establishment of many diseases, such as cancer, diabetes, cardiovascular disease, and neurodegeneration. Many transcription factors have been shown to be modified by O-linked GlcNAc modification, which can influence their transcriptional activity, DNA binding, localization, stability, and interaction with other co-factors. This review focuses on modulation of transcription factor function by O-linked GlcNAc modification.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetylglucosamine / chemistry*
  • Acetylglucosamine / metabolism*
  • Active Transport, Cell Nucleus
  • Animals
  • Cyclic AMP Response Element-Binding Protein / chemistry
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Glycosylation
  • Humans
  • Models, Biological
  • N-Acetylglucosaminyltransferases / metabolism
  • NF-kappa B / chemistry
  • NF-kappa B / metabolism
  • Protein Interaction Domains and Motifs
  • Protein Processing, Post-Translational
  • Protein Stability
  • Receptors, Estrogen / chemistry
  • Receptors, Estrogen / metabolism
  • STAT5 Transcription Factor / chemistry
  • STAT5 Transcription Factor / metabolism
  • Trans-Activators / chemistry
  • Trans-Activators / metabolism
  • Transcription Factors / chemistry*
  • Transcription Factors / metabolism*
  • Tumor Suppressor Protein p53 / chemistry
  • Tumor Suppressor Protein p53 / metabolism
  • YY1 Transcription Factor / chemistry
  • YY1 Transcription Factor / metabolism
  • beta-N-Acetylhexosaminidases / metabolism

Substances

  • Cyclic AMP Response Element-Binding Protein
  • NF-kappa B
  • Receptors, Estrogen
  • STAT5 Transcription Factor
  • Trans-Activators
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • YY1 Transcription Factor
  • N-Acetylglucosaminyltransferases
  • O-GlcNAc transferase
  • hexosaminidase C
  • beta-N-Acetylhexosaminidases
  • Acetylglucosamine