Li Robert, Jia Zhenquan, Zhu Hong
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.
React Oxyg Species (Apex). 2019 Nov;8(24):312-322.
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.
抗氧化基因表达的调控对于控制氧化应激和维持生理稳态至关重要。在此背景下，核因子E2相关因子2（Nrf2）已被确定为多种抗氧化基因以及许多其他细胞保护基因转录的主要调节因子。Nrf2的活性在蛋白质稳定性、转录和转录后等多个水平受到调控。在各种调控途径中，Keap1-Cul3-Rbx1轴是Nrf2活性最突出的调节因子。作为抗氧化基因严格控制的转录激活因子，Nrf2信号通路与健康和疾病密切相关。虽然Nrf2是抵抗氧化和亲电子组织损伤的保护因子，但Nrf2信号通路的持续激活也可能导致疾病病理生理学，如癌症进展。
