Research Article

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

  • Wan-Chen HuangAffiliated withDepartment of Pharmacology, College of Medicine, National Cheng Kung University
  • , Shu-Ting ChenAffiliated withDepartment of Pharmacology, College of Medicine, National Cheng Kung University
  • , Wei-Chiao ChangAffiliated withGraduate Institute of Medical Genetics, Kaohsiung Medical UniversityCancer Center, Kaohsiung Medical University Hospital
  • , Kwang-Yu ChangAffiliated withNational Institute of Cancer Research, National Health Research Institutes
  • , Wen-Chang ChangAffiliated withDepartment of Pharmacology, College of Medicine, National Cheng Kung UniversityCenter for Gene Regulation and Signal Transduction Research, National Cheng Kung UniversityInstitute of Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University Email author 
  • , Ben-Kuen ChenAffiliated withDepartment of Pharmacology, College of Medicine, National Cheng Kung UniversityCenter for Gene Regulation and Signal Transduction Research, National Cheng Kung UniversityInstitute of Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University Email author 

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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 p21 WAF1/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