Dynamic glycosylation of the transcription factor CREB: a potential role in gene regulation

J Am Chem Soc. 2003 Jun 4;125(22):6612-3. doi: 10.1021/ja028200t.

Abstract

We report that CREB (cyclic AMP-responsive element-binding protein), a transcription factor essential for long-term memory, is O-GlcNAc glycosylated in the mammalian brain. Glycosylation occurs at two sites within the Q2 domain and disrupts the interaction between CREB and TAFII130, thereby repressing the transcriptional activity of CREB in vitro. These findings have important implications for the role of O-GlcNAc glycosylation in gene regulation, and they provide a link between O-GlcNAc and information storage processes in the brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / chemistry
  • Acetylglucosamine / metabolism
  • Animals
  • Brain / metabolism
  • Brain / physiology
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Cyclic AMP Response Element-Binding Protein / physiology
  • Gene Expression Regulation / physiology*
  • Glycosylation
  • HeLa Cells
  • Humans
  • N-Acetyllactosamine Synthase / chemistry
  • N-Acetyllactosamine Synthase / metabolism
  • Rats
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • TATA-Binding Protein Associated Factors / metabolism
  • TATA-Binding Protein Associated Factors / physiology
  • Transcription Factor TFIID / metabolism
  • Transcription Factor TFIID / physiology
  • Transcriptional Activation / physiology

Substances

  • Cyclic AMP Response Element-Binding Protein
  • TAF4 protein, human
  • TATA-Binding Protein Associated Factors
  • Transcription Factor TFIID
  • N-Acetyllactosamine Synthase
  • Acetylglucosamine