REVIEW: Mazes of Nrf2 Regulation

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N. K. Zenkov¹, P. M. Kozhin¹, A. V. Chechushkov¹, G. G. Martinovich², N. V. Kandalintseva³, and E. B. Menshchikova^1*

¹Research Institute of Experimental and Clinical Medicine, 630117 Novosibirsk, Russia; E-mail: lemen@centercem.ru

²Belarusian State University, 220030 Minsk, Belarus; E-mail: martinovichgg@bsu.by

³Novosibirsk State Pedagogical University, 630126 Novosibirsk, Russia; E-mail: nspu@nspu.net

^* To whom correspondence should be addressed.

Received December 8, 2016; Revision received December 27, 2016

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Nrf2 transcription factor plays a key role in maintaining cellular redox balance under stress and is a perspective target for oxidative stress-associated diseases. Under normal conditions, Nrf2 transcriptional activity is low due to its rapid ubiquitination and degradation in the 26S proteasome, as well as through various modifications of amino acid residues of this transcription factor that regulate its transport to the nucleus and binding to DNA. Continuous activation of Nrf2 is possible due to autophagy and epigenetic regulation that may underlie the increased resistance of tumor cells to radiotherapy and chemotherapy. This review deals with the mechanisms of regulation of Nrf2 transcriptional activity and its main elements, and pharmacological approaches to activation of the Keap1/Nrf2/ARE system.

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KEY WORDS: Nrf2 transcription factor, ubiquitination, autophagy, epigenetic regulation

DOI: 10.1134/S0006297917050030

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