Independent and cooperative activation of chromosomal c-fos promoter by STAT3

J Biol Chem. 2003 May 2;278(18):15794-9. doi: 10.1074/jbc.M213073200. Epub 2003 Feb 24.


The c-fos gene was one of the earliest vertebrate genes shown to be transcriptionally induced by growth factors. Intensive study of the promoter of c-fos (-325 to -80) by transient or permanent transfections of synthetic DNA constructs has repeatedly shown the importance of several sequence elements and the resident nuclear proteins that bind them (e.g. ternary complex factor/ELK1; serum response factor, cAMP response element-binding protein/amino-terminal fragment/AP-1). However these studies have left unanswered numerous questions about the role of these proteins in the regulation of the native chromosomal gene. In particular, the role of a site in this enhancer that binds STATs has been controversial. We present evidence here that STAT3 and not STAT1 accumulates on the chromosomal c-fos promoter and provides a boost to transcription without the activation of resident nuclear proteins through serine kinases. Also, when resident nuclear proteins such as ELK1 are activated to varying extents by mitogen-activated protein kinase pathways, STAT3 activation provides a 2-fold boost regardless of the final level of activated transcription. Thus the several proteins that interact with the c-fos enhancer apparently can act either in a cooperative or independent manner to achieve very different levels of transcription.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • DNA / metabolism
  • DNA-Binding Proteins / physiology*
  • Genes, fos*
  • Humans
  • Interleukin-6 / physiology
  • Mitogen-Activated Protein Kinases / physiology
  • Promoter Regions, Genetic*
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • Trans-Activators / physiology*


  • DNA-Binding Proteins
  • Interleukin-6
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Trans-Activators
  • DNA
  • Mitogen-Activated Protein Kinases