Biochemistry (Moscow)

, Volume 78, Issue 2, pp 111–126 | Cite as

Keap1-Nrf2 signaling pathway: Mechanisms of regulation and role in protection of cells against toxicity caused by xenobiotics and electrophiles

  • K. T. TurpaevEmail author


The transcription factor Nrf2 governs the expression of a considerable group of genes involved in cell protection against oxidants, electrophiles, and genotoxic compounds. The activity of Nrf2 is sensitive to xenobiotics and endogenous electrophiles. Nrf2 is negatively regulated by specific suppressor protein Keap1, which is also a receptor of electrophiles and adapter for Cul3 ubiquitin ligase. Electrophiles react with critical thiol groups of Keap1 leading to the loss of its ability to inhibit Nrf2. The Keap1-Nrf2 signaling pathway also down-regulates NF-κB transcriptional activity and attenuates cytokine-mediated induction of proinflammatory genes. Pharmacological activation of the Keap1-Nrf2 pathway can be used for treatment and prevention of many diseases. Widely known natural Keap1-Nrf2 activators include curcumin, quercetin, resveratrol, and sulforaphane. The most effective Keap1-Nrf2 activators are synthetic oleanane triterpenoids.

Key words

protective genes xenobiotics thiols electrophiles Keap1 Nrf2 



aldo-keto reductase


antioxidant response element


cAMP-responsive element-binding protein-binding protein (protein that binds the protein binding to the cAMP sensitive regulatory region)


cyclooxygenase 2


15-deoxy-Δ12,14-prostaglandin J2


glycogen synthase kinase 3




heme oxygenase 1


inducible nitric oxide synthase


multidrug resistant protein


NAD(P)H:quinone oxidoreductase 1


peroxisome proliferator-activated receptor γ




reactive oxygen species


serum- and glucocorticoid-induced protein kinase 1




xenobiotic response element (the regulatory region sensitive to xenobiotics)


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Copyright information

© Pleiades Publishing, Ltd. 2013

Authors and Affiliations

  1. 1.Center for Theoretical Problems of Physicochemical PharmacologyRussian Academy of SciencesMoscowRussia

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