Modulation of transcription factor function by O-GlcNAc modification

Sabire Özcan, Sreenath S. Andrali, Jamie E.L. Cantrell

Research output: Contribution to journalReview articlepeer-review

201 Scopus citations

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.

Original languageEnglish
Pages (from-to)353-364
Number of pages12
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume1799
Issue number5-6
DOIs
StatePublished - 2010

Bibliographical note

Funding Information:
We apologize to all authors, whose original publications could not be cited or discussed in this review due to space limitations. We thank the reviewers for their insightful comments. Research in the corresponding author's laboratory was supported by grants R01DK067581 from the NIH/NIDDK , P20RR020171 from NIH/NCRR , and 1-05-CD-15 from the American Diabetes Association .

Keywords

  • Hexosamine
  • O-GlcNAc
  • OGA
  • OGT
  • Transcription
  • Transcription factor

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics

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