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Publications

Journal Article Review Epublish

PubMed: 40765830 DOI: 10.7150/ijbs.112869

New insights into coordinated regulation of AHR promoter transcription; molecular mechanisms and therapeutic targets.

Int J Biol Sci 21(10):4504-4528

Authors: Kenly Wuputra, Chia-Che Ku, Wen-Hung Hsu, Tusty-Jiuan Hsieh, Yi-Chun Tsai, Chih-Yen Chen, Yoshiharu Tanaka, Ying-Chu Lin, Chao-Hung Kuo, Deng-Chyang Wu, Kazunari K Yokoyama

Affiliations

  • Cell Therapy Research Center, Department of Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan.
  • Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
  • Regenerative Medicine and Cell Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
  • Cell Therapy Research Center, Department of Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan. Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. Regenerative Medicine and Cell Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
  • Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan.
  • Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University GangShan Hospital, Kaohsiung 820004, Taiwan.
  • Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan.
  • Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University CiJin Hospital, Kaohsiung 805, Taiwan.
  • Institute of Emergency and Critical Medicine, and School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan.
  • Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112201, Taiwan.
  • Radiation Biology and Molecular Genetics, Division of Quantum Radiation, Faculty of Technology, Osaka Metropolitan University, Osaka 599-8531, Japan.
  • School of Dentistry, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.

Abstract

The aryl hydrocarbon receptor (AHR) plays crucial roles in the control of stress, xenobiotic metabolism, inflammation, and cancer. However, information on the chromatin regulation of ligand-dependent AHR promoter activation is limited. AHR and nuclear factor erythroid 2-related factor 2 (NRF2) signaling are coordinated to maintain the balance of reactive oxygen species (ROS), which is termed the AHR-NRF2 gene battery. Recently, promoter activation of AHR to phase I ligands was reported to be regulated by AHR-NRF2-Jun dimerization protein 2 (JDP2) in a spatiotemporal manner. Tight coupling between phase I and II nuclear transcriptional factor complexes through histone chaperone JDP2 in a time- and space-dependent manner may occur in the chromatin to regulate phase I gene expression. This new mechanism, termed AHR-NRF2-JDP2 gene battery, may facilitate the identification of therapeutics at the reduction of reactive toxic intermediates at the nucleosome level. Identifying the AHR-NRF2-JDP2 gene battery mechanisms will enable the development of novel therapeutics for the risk assessment of oxidative stress/antioxidation, detoxification, ROS, cell death, inflammation, allergies, and cancer.

MeSH

Genes, Receptors, Aryl Hydrocarbon, Promoter Regions, Genetic, Stress, Physiological, Neoplasms, Chromatin, Therapeutics, Ligands