Regulation of FoxO activity by CBP/p300-mediated acetylation

Trends Biochem Sci. 2005 Feb;30(2):81-6. doi: 10.1016/j.tibs.2004.12.002.


Forkhead box, class O (FoxO) transcription factors are inhibited by insulin-induced FoxO phosphorylation. Recently, acetylation of FoxO factors by calcium response element-binding (CREB)-binding protein (CBP) and/or p300 has been identified as a novel regulatory pathway, although the exact consequences of acetylation remain unclear. We propose that binding of CBP/p300 to FoxO factors is essential for FoxO-mediated transcription. CBP and p300 act as FoxO cofactors by weakening histone-DNA interactions. Acetylation of FoxO factors, however, attenuates FoxO-mediated transcriptional activity by disrupting the interaction between FoxO factors and target DNA. Therefore, acetylation shifts the function of FoxO from cell-cycle arrest and protection against oxidative stress towards cell death.

MeSH terms

  • Acetylation
  • Animals
  • CREB-Binding Protein
  • DNA / metabolism
  • Forkhead Transcription Factors
  • Growth Substances / metabolism
  • Histone Deacetylases / metabolism
  • Histones / metabolism
  • Humans
  • Insulin / metabolism
  • Models, Biological
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / physiology*
  • Phosphorylation
  • Protein Binding
  • Sirtuins / metabolism
  • Trans-Activators / metabolism
  • Trans-Activators / physiology*
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*


  • Forkhead Transcription Factors
  • Growth Substances
  • Histones
  • Insulin
  • Nuclear Proteins
  • Trans-Activators
  • Transcription Factors
  • DNA
  • CREB-Binding Protein
  • CREBBP protein, human
  • Sirtuins
  • Histone Deacetylases