Regulation of Nrf2-Mediated Phase II Detoxification and Anti-oxidant Genes

• Published in: Biomolecules & therapeutics Vol. 20; no. 2; pp. 144 - 151
• Main Author: Keum, Young-Sam
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Society of Applied Pharmacology 01.03.2012; 한국응용약물학회
• Subjects: 약학; Kelch-like ECH-associated protein 1 (Keap1); Antioxidant Response Element (ARE); NF-E2-related Factor-2 (Nrf2); Chemoprevention
• ISSN: 1976-9148; 2005-4483
• DOI: 10.4062/biomolther.2012.20.2.144

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.