REVIEW: Mechanism of the Nrf2/Keap1/ARE Signaling System

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V. O. Tkachev^1,2*, E. B. Menshchikova¹, and N. K. Zenkov¹

¹Scientific Center of Clinical and Experimental Medicine, Siberian Branch of the Russian Academy of Medical Sciences, ul. Timakova 2, 630117 Novosibirsk, Russia; fax: (383) 333-6456; E-mail: tkachev_victor@mail.ru

²Institute of Clinical Immunology, Siberian Branch of the Russian Academy of Medical Sciences, ul. Yadrintsevskaya 14, 630094 Novosibirsk, Russia; fax: (383) 236-0329; E-mail: v_kozlov@online.nsk.su

^* To whom correspondence should be addressed.

Received August 27, 2010; Revision received September 20, 2010

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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 interconnection 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.

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KEY WORDS: redox regulation, Nrf2, Keap1, antioxidant-respons(iv)e element (ARE)

DOI: 10.1134/S0006297911040031

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