The Immediate Early Genes Fos and Egr1 Become STAT1 Transcriptional Targets in the Absence of STAT3

FEBS Lett. 2011 Aug 4;585(15):2455-60. doi: 10.1016/j.febslet.2011.06.020. Epub 2011 Jun 28.

Abstract

Signal transducer and activators of transcription (STAT)1 and STAT3 cross-regulate their activity downstream of gp130 cytokines, and eliminating STAT3 leads to IFN-γ-like responses to IL-6 correlating with prolonged STAT1 phosphorylation. Here we demonstrate that the increased gp130-mediated induction of the IFN-γ-responsive interferon regulatory factor 1 gene observed in STAT3(-/-) cells correlates with prolonged STAT1 binding to its promoter. Intriguingly, gp130-mediated induction of the immediate early genes FBJ osteosarcoma oncogene and early growth response 1 is also prolonged in STAT3(-/-) cells, with STAT1 binding to their promoters. Thus the abrogation of STAT3 expression, perturbing the signaling balance, directs the STAT1 oncosuppressor to transcribe new target genes, known to drive mitogen responses and tumor transformation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cytokine Receptor gp130
  • Early Growth Response Protein 1 / genetics*
  • Genes, Immediate-Early / genetics*
  • Genes, fos / genetics*
  • Mice
  • Mice, Knockout
  • Promoter Regions, Genetic
  • STAT1 Transcription Factor / genetics*
  • STAT3 Transcription Factor / deficiency*
  • Transcription, Genetic

Substances

  • Early Growth Response Protein 1
  • Egr1 protein, mouse
  • Il6st protein, mouse
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • Stat1 protein, mouse
  • Stat3 protein, mouse
  • Cytokine Receptor gp130