Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Regulation of Nrf2-Mediated Phase II Detoxification and Anti-oxidant Genes

  • Keum, Young-Sam (Department of Biochemistry, College of Pharmacy, Dongguk University)
  • Received : 2011.04.12
  • Accepted : 2011.08.17
  • Published : 2012.03.31
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Abstract

The molecular mechanisms by which a variety of naturally-occurring dietary compounds exert chemopreventive effects have been a subject of intense scientific investigations. Induction of phase II detoxification and anti-oxidant enzymes through activation of Nrf2/ARE-dependent gene is recognized as one of the major cellular defense mechanisms against oxidative or xenobiotic stresses and currently represents a critical chemopreventive mechanism of action. In the present review, the functional significance of Keap1/Nrf2 protein module in regulating ARE-dependent phase II detoxification and anti-oxidant gene expression is discussed. The biochemical mechanisms underlying the phosphorylation and expression of Keap1/Nrf2 proteins that are controlled by the intracellular signaling kinases and ubiquitin-mediated E3 ligase system as well as control of nucleocytoplasmic translocation of Nrf2 by its innate nuclear export signal (NES) are described.

Keywords

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