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KMID : 0606920120200020144
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Biomolecules & Therapeutics
2012 Volume.20 No. 2 p.144 ~ p.151
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Regulation of Nrf2-Mediated Phase II Detoxification and Anti-oxidant Genes
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Keum Young-Sam
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Abstract
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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.
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KEYWORD
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Chemoprevention, NF-E2-related Factor-2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), Antioxidant Response Element (ARE)
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