Jacqui Wood Cancer Centre, Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK.
Jacqui Wood Cancer Centre, Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK.
Trends Biochem Sci. 2014 Apr;39(4):199-218. doi: 10.1016/j.tibs.2014.02.002. Epub 2014 Mar 16.
Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2, also called Nfe2l2) is a transcription factor that regulates the cellular redox status. Nrf2 is controlled through a complex transcriptional/epigenetic and post-translational network that ensures its activity increases during redox perturbation, inflammation, growth factor stimulation and nutrient/energy fluxes, thereby enabling the factor to orchestrate adaptive responses to diverse forms of stress. Besides mediating stress-stimulated induction of antioxidant and detoxification genes, Nrf2 contributes to adaptation by upregulating the repair and degradation of damaged macromolecules, and by modulating intermediary metabolism. In the latter case, Nrf2 inhibits lipogenesis, supports β-oxidation of fatty acids, facilitates flux through the pentose phosphate pathway, and increases NADPH regeneration and purine biosynthesis; these observations suggest Nrf2 directs metabolic reprogramming during stress.
核因子红细胞 2 相关因子 2(Nrf2,也称为 Nfe2l2)是一种转录因子,可调节细胞氧化还原状态。Nrf2 通过复杂的转录/表观遗传和翻译后网络进行调控,以确保其在氧化还原应激、炎症、生长因子刺激和营养/能量通量期间活性增加,从而使该因子能够协调对各种形式的应激的适应性反应。除了介导应激刺激的抗氧化和解毒基因的诱导外,Nrf2 通过上调受损大分子的修复和降解以及调节中间代谢来促进适应。在后一种情况下,Nrf2 抑制脂肪生成,支持脂肪酸的β氧化,促进通过磷酸戊糖途径的通量,并增加 NADPH 的再生和嘌呤生物合成;这些观察结果表明,Nrf2 在应激期间指导代谢重编程。