An important role of Nrf2-ARE pathway in the cellular defense mechanism.
The antioxidant responsive element (ARE) is a cis-acting regulatory element of genes encoding phase II detoxification enzymes and antioxidant proteins, such as NAD(P)H: quinone oxidoreductase 1, glutathione S-transferases, and glutamate-cysteine ligase. Interestingly, it has been reported that Nrf2 (NF-E2-related factor 2) regulates a wide array of ARE-driven genes in various cell types. Nrf2 is a basic leucine zipper transcription factor, which was originally identified as a binding protein of locus control region of beta-globin gene. The DNA binding sequence of Nrf2 and ARE sequence are very similar, and many studies demonstrated that Nrf2 binds to the ARE sites leading to up-regulation of downstream genes. The function of Nrf2 and its downstream target genes suggests that the Nrf2-ARE pathway is important in the cellular antioxidant defense system. In support of this, many studies showed a critical role of Nrf2 in cellular protection and anti-carcinogenicity, implying that the Nrf2-ARE pathway may serve as a therapeutic target for neurodegenerative diseases and cancers, in which oxidative stress is closely implicated.
Lee
Jong-Min
JM
School of Pharmacy, University of Wisconsin, Madison, WI 53705, USA.
Johnson
Jeffrey A
JA
D000818:Animals; D019610:Cytoprotection; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007111:Immunity, Cellular; D016350:Leucine Zippers / Q000235:genetics; D008954:Models, Biological; D051267:NF-E2-Related Factor 2; D020218:Response Elements; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology* / Q000502:physiology*
D004268:DNA-Binding Proteins; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D015534:Trans-Activators