Retinoid-dependent antagonism of serum response factor transactivation mediated by transcriptional coactivator proteins

Oncogene. 2001 Oct 4;20(45):6638-42. doi: 10.1038/sj.onc.1204695.


Transcriptional coactivators SRC-1 and p300 specifically interact with liganded-nuclear receptors and also modulate other transcription factors, including serum response factor (SRF). Here, we report that retinoids repress transactivation by SRF and specific interactions exist between the DNA binding domains of SRF and retinoic acid and retinoid X receptors. We further demonstrate that the repression may involve retinoid-dependent competition for a limiting amount of SRC-1 and p300 between SRF and retinoid receptors. We propose that the well-defined anti-proliferative action of retinoids could, at least in part, result from this novel transrepressive action on the mitogenic transcription factor SRF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alitretinoin
  • Animals
  • Cell Division
  • Cells, Cultured
  • DNA-Binding Proteins / antagonists & inhibitors*
  • DNA-Binding Proteins / metabolism
  • E1A-Associated p300 Protein
  • HeLa Cells
  • Histone Acetyltransferases
  • Humans
  • Models, Genetic
  • Nuclear Proteins / antagonists & inhibitors*
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / physiology*
  • Nuclear Receptor Coactivator 1
  • Rats
  • Receptors, Retinoic Acid / metabolism
  • Serum Response Factor
  • Trans-Activators / physiology*
  • Transcription Factors / physiology*
  • Transcriptional Activation*
  • Tretinoin / pharmacology*


  • DNA-Binding Proteins
  • Nuclear Proteins
  • Receptors, Retinoic Acid
  • Serum Response Factor
  • Trans-Activators
  • Transcription Factors
  • Alitretinoin
  • Tretinoin
  • E1A-Associated p300 Protein
  • Ep300 protein, rat
  • Histone Acetyltransferases
  • NCOA1 protein, human
  • Nuclear Receptor Coactivator 1