RelB, a new partner of aryl hydrocarbon receptor-mediated transcription

Mol Endocrinol. 2007 Dec;21(12):2941-55. doi: 10.1210/me.2007-0211. Epub 2007 Sep 6.

Abstract

The nuclear factor-kappaB (NF-kappaB) transcription factor family has a crucial role in rapid responses to stress and pathogens. We show that the NF-kappaB subunit RelB is functionally associated with the aryl hydrocarbon receptor (AhR) and mediates transcription of chemokines such as IL-8 via activation of AhR and protein kinase A. RelB physically interacts with AhR and binds to an unrecognized RelB/AhR responsive element of the IL-8 promoter linking two signaling pathways to activate gene transcription. We found a time-dependent recruitment of AhR to the RelB/AhR responsive element site of IL-8 mediated by the AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) and via activation of protein kinase A. Furthermore, NF-kappaB-binding sites that are preferentially recognized by RelB/p52 are a target for RelB/AhR complexes without addition of any stimuli, implicating the endogenous function of the AhR. RelB/AhR complexes are also found to bind on xenobiotic responsive element, and RelB drastically increases the 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced xenobiotic responsive element reporter activity. The interaction of RelB with AhR signaling, and AhR with NF-kappaB RelB signaling pathways represent a new mechanism of cross talk between the two transcription factors.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Binding Sites
  • Cell Line, Tumor
  • Colforsin / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Humans
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • Polychlorinated Dibenzodioxins / pharmacology
  • Promoter Regions, Genetic
  • Protein Binding
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Response Elements
  • Signal Transduction / drug effects
  • Transcription Factor RelB / genetics
  • Transcription Factor RelB / metabolism*
  • Transcription, Genetic / genetics*

Substances

  • Interleukin-8
  • NF-kappa B
  • Polychlorinated Dibenzodioxins
  • RELB protein, human
  • Receptors, Aryl Hydrocarbon
  • Transcription Factor RelB
  • Colforsin
  • Cyclic AMP-Dependent Protein Kinases