Mechanism of the Nrf2/Keap1/ARE signaling system

• Published in: Biochemistry (Moscow) Vol. 76; no. 4; pp. 407 - 422
• Main Authors: Tkachev, V. O., Menshchikova, E. B., Zenkov, N. K.
• Format: Journal Article
• Language: English
• Published: Dordrecht SP MAIK Nauka/Interperiodica 01.04.2011; Springer; Springer Nature B.V
• Subjects: Amino acids; Animals; Binding sites; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; DNA binding proteins; Gene Expression; Gene Expression Regulation; Genes; Genetic transcription; Humans; Inactivation; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Kelch-Like ECH-Associated Protein 1; Life Sciences; Microbiology; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; Oxidation-Reduction; Oxidative Stress; Post-translational modification; Protein Conformation; Response Elements - genetics; Review; Signal Transduction; Translocation; Keap1; redox regulation; antioxidant-respons(iv)e element (ARE); Nrf2
• ISSN: 0006-2979; 1608-3040
• DOI: 10.1134/S0006297911040031

Nrf2 regulates expression of genes containing antioxidant-respons(iv)e element (ARE) in their promoters and plays a pivotal role among all redox-sensitive transcription factors. Nrf2 is constitutively controlled by repressor protein Keap1, which acts as a molecular sensor of disturbances in cellular homeostasis. These molecular patterns are in close inter-connection and function as parts of the integrated redox-sensitive signaling system Nrf2/Keap1/ARE. Depending on cellular redox balance, activity of this signaling system changes at the levels of transcription, translation, posttranslational modification, nuclear translocation of transcription factor, and its binding to ARE-driven gene promoters. This review summarizes current conceptions of Nrf2/Keap1/ARE induction and inactivation.