Zenkov N K, Kozhin P M, Chechushkov A V, Martinovich G G, Kandalintseva N V, Menshchikova E B
Research Institute of Experimental and Clinical Medicine, Novosibirsk, 630117, Russia.
Biochemistry (Mosc). 2017 May;82(5):556-564. doi: 10.1134/S0006297917050030.
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转录因子在应激状态下维持细胞氧化还原平衡中起关键作用，是氧化应激相关疾病的一个有前景的靶点。在正常条件下，Nrf2的转录活性较低，这是因为它在26S蛋白酶体中迅速泛素化和降解，以及通过该转录因子氨基酸残基的各种修饰来调节其向细胞核的转运和与DNA的结合。由于自噬和表观遗传调控，Nrf2的持续激活是可能的，这可能是肿瘤细胞对放疗和化疗耐药性增加的基础。本文综述了Nrf2转录活性的调控机制及其主要元件，以及激活Keap1/Nrf2/ARE系统的药理学方法。
