Cellular and Molecular Life Sciences

, Volume 67, Issue 20, pp 3523–3533

Involvement of aryl hydrocarbon receptor nuclear translocator in EGF-induced c-Jun/Sp1-mediated gene expression

Authors

  • Wan-Chen Huang
    • Department of Pharmacology, College of MedicineNational Cheng Kung University
  • Shu-Ting Chen
    • Department of Pharmacology, College of MedicineNational Cheng Kung University
  • Wei-Chiao Chang
    • Graduate Institute of Medical GeneticsKaohsiung Medical University
    • Cancer CenterKaohsiung Medical University Hospital
  • Kwang-Yu Chang
    • National Institute of Cancer ResearchNational Health Research Institutes
    • Department of Pharmacology, College of MedicineNational Cheng Kung University
    • Center for Gene Regulation and Signal Transduction ResearchNational Cheng Kung University
    • Institute of Biosignal Transduction, College of Bioscience and BiotechnologyNational Cheng Kung University
    • Department of Pharmacology, College of MedicineNational Cheng Kung University
    • Center for Gene Regulation and Signal Transduction ResearchNational Cheng Kung University
    • Institute of Biosignal Transduction, College of Bioscience and BiotechnologyNational Cheng Kung University
Research Article

DOI: 10.1007/s00018-010-0392-9

Cite this article as:
Huang, W., Chen, S., Chang, W. et al. Cell. Mol. Life Sci. (2010) 67: 3523. doi:10.1007/s00018-010-0392-9

Abstract

Aryl hydrocarbon receptor nuclear translocator (ARNT) binds to other basic helix-loop-helix Per/ARNT/Sim (bHLH-PAS) proteins to form functional transcriptional complexes in order to regulate specific biological pathways. Here, we report a novel mechanism that upon EGF treatment, ARNT associated with non-bHLH-PAS transcription factors, c-Jun/Sp1, and regulated gene expression, through forming a c-Jun/ARNT/Sp1 complex and binding to the Sp1 site of the gene promoter. EGF-induced promoter activity and the mRNA level of 12(S)-lipoxygenase as well as the association between c-Jun and Sp1 were reduced by ARNT knockdown. Notably, dominant negative c-Jun mutant, TAM-67, blocked ARNT-mediated 12(S)-lipoxygenase expression, demonstrating that c-Jun was responsible for the transcriptional activation. Moreover, ARNT knockdown also inhibited other EGF-induced c-Jun/Sp1 mediated gene expression, such as p21WAF1/CIP1. Our results reveal a novel mechanism by which ARNT acts as a modulator to bridge the c-Jun/Sp1 interaction and plays a role in EGF-mediated gene expression under normoxic conditions.

Keywords

Epidermal growth factor (EGF)Aryl hydrocarbon receptor nuclear translocator (ARNT)Gene expressionc-Jun/Sp1Protein–DNA interaction

Supplementary material

18_2010_392_MOESM1_ESM.ppt (126 kb)
Supplementary Figures (PPT 126 kb)

Copyright information

© Springer Basel AG 2010