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. 2019 Aug 8;20(16):3856. doi: 10.3390/ijms20163856

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© 2019 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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The nuclear factor-erythroid 2-related factor 2 (NRF2) signaling pathway. NRF2 strongly binds to its cytoplasmic inhibitor Kelch-like ECH-associated protein 1 (KEAP1) under homeostatic conditions and only low levels of NRF2 are present in the nucleus. In response to reactive oxygen species (ROS) and/or electrophiles, the NRF2-KEAP1 interaction is weakened and newly formed NRF2 accumulates in the nucleus. Here, NRF2 dimerizes with small musculoaponeurotic fibrosarcoma (MAF) proteins and binds to antioxidant response elements (AREs) in the promoters or enhancers of its target genes, of which many encode ROS detoxifying enzymes and other antioxidant proteins, thereby initiating a cytoprotective response.