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React Oxyg Species (Apex). 2019 Nov;8(24):312-322.

Regulation of Nrf2 Signaling.

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Department of Pharmacology, Campbell University School of Osteopathic Medicine, Buies Creek, NC 27506, USA.
Department of Biology, University of North Carolina, Greensboro, NC 27412, USA.
Department of Physiology and Pathophysiology, Campbell University School of Osteopathic Medicine, Buies Creek, NC 27506, USA.


Regulation of antioxidant gene expression is essential for controlling oxidative stress and maintaining physiological homeostasis. In this context, the nuclear factor E2-related factor 2 (Nrf2) has been identified as the chief regulator of the transcription of diverse antioxidant genes as well as many other cytoprotective genes. Nrf2 activity is subjected to the regulation at various levels including protein stability, transcription, and post-transcription. Among the various regulatory pathways, the Keap1-Cul3-Rbx1 axis is the most prominent regulator of Nrf2 activity. Being a tightly controlled transcriptional activator of antioxidant genes, Nrf2 signaling is intimately involved in health and disease. While Nrf2 is a protector against oxidative and electrophilic tissue injury, persistent activation of Nrf2 signaling may also contribute to disease pathophysiology, such as cancer progression.


Antioxidant; Antioxidant response element; Aromatic hydrocarbon receptor; Gene regulation; Keap1; MicroRNA; NF-κB; Nrf2; Reactive oxygen species; p53; p62


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