Biochemistry (Moscow)

, Volume 82, Issue 5, pp 556–564 | Cite as

Mazes of Nrf2 regulation

  • N. K. Zenkov
  • P. M. Kozhin
  • A. V. Chechushkov
  • G. G. Martinovich
  • N. V. Kandalintseva
  • E. B. MenshchikovaEmail author


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.


Nrf2 transcription factor ubiquitination autophagy epigenetic regulation 



protein kinase B


adenosine monophosphate-activated protein kinase


atypical protein kinase C


antioxidant response element)


Broad-complex (Tramtrack, Bric-a-brac)


basic leucine zipper DNA-binding domain




extracellular signal-regulated protein kinase 1/2


farnesoid X receptor


glycogen synthase kinase 3


tyrosine protein kinase of EGFR/ErbB receptor family


β-subunit of IκB-kinase


tyrosine kinase Janus kinase/signal transducer and activator of transcription


kinases of MAPK family (c-Jun N-terminal kinases)


Kelch-like ECH-associated protein 1


Keap-interacting region


microtubule-associated protein 1A/1B-light chain 3


LC3 interacting region


mitogen-activated protein kinases


mammalian target of rapamycin (a serine/threonine protein kinase)


mammalian target of rapamycin complex 1/2


Nrf2-ECH homology (ECH is a homolog of Nrf2 in chickens)


nuclear export signal


nuclear factor-erythroid derived


nuclear localization signal


NF-E2-related factor 2


Phox and Bem1


protein kinase-like endoplasmic reticulum kinase


serine/threonine phosphatase (phosphoglycerate mutase family, member 5)


phosphatidylinositol 3-kinase


protein kinase C

p38 MAPK

p38 mitogen activated protein kinase


receptor binding peroxisome proliferators (peroxisome proliferator-activated receptor γ)


ubiquitin-binding protein p62, same as sequestosome 1


dual-specificity protein phosphatase (phosphatase and tensin homolog deleted on chromosome 10)


RING-box protein 1


reactive oxygen species


retinoid X receptor α


TNFα receptor-associated factor 6


β-transducin repeat containing protein


ubiquitin association


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Copyright information

© Pleiades Publishing, Ltd. 2017

Authors and Affiliations

  • N. K. Zenkov
    • 1
  • P. M. Kozhin
    • 1
  • A. V. Chechushkov
    • 1
  • G. G. Martinovich
    • 2
  • N. V. Kandalintseva
    • 3
  • E. B. Menshchikova
    • 1
    Email author
  1. 1.Research Institute of Experimental and Clinical MedicineNovosibirskRussia
  2. 2.Belarusian State UniversityMinskBelarus
  3. 3.Novosibirsk State Pedagogical UniversityNovosibirskRussia

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