Cellular and Molecular Life Sciences

, Volume 67, Issue 20, pp 3523–3533 | Cite as

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

Research Article

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 expression c-Jun/Sp1 Protein–DNA interaction 

Supplementary material

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

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Copyright information

© Springer Basel AG 2010

Authors and Affiliations

  • Wan-Chen Huang
    • 1
  • Shu-Ting Chen
    • 1
  • Wei-Chiao Chang
    • 2
    • 6
  • Kwang-Yu Chang
    • 3
  • Wen-Chang Chang
    • 1
    • 4
    • 5
  • Ben-Kuen Chen
    • 1
    • 4
    • 5
  1. 1.Department of Pharmacology, College of MedicineNational Cheng Kung UniversityTainanTaiwan, ROC
  2. 2.Graduate Institute of Medical GeneticsKaohsiung Medical UniversityKaohsiungTaiwan, ROC
  3. 3.National Institute of Cancer ResearchNational Health Research InstitutesTainanTaiwan, ROC
  4. 4.Center for Gene Regulation and Signal Transduction ResearchNational Cheng Kung UniversityTainanTaiwan, ROC
  5. 5.Institute of Biosignal Transduction, College of Bioscience and BiotechnologyNational Cheng Kung UniversityTainanTaiwan, ROC
  6. 6.Cancer CenterKaohsiung Medical University HospitalKaohsiungTaiwan, ROC

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