Nguyen Truyen, Sherratt Philip J, Pickett Cecil B
Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA.
Annu Rev Pharmacol Toxicol. 2003;43:233-60. doi: 10.1146/annurev.pharmtox.43.100901.140229. Epub 2002 Jan 10.
The expression of genes encoding antioxidative and Phase II detoxification enzymes is induced in cells exposed to electrophilic compounds and phenolic antioxidants. Induction of these enzymes is regulated at the transcriptional level and is mediated by a specific enhancer, the antioxidant response element or ARE, found in the promoter of the enzyme's gene. The transcription factor Nrf2 has been implicated as the central protein that interacts with the ARE to activate gene transcription constitutively or in response to an oxidative stress signal. This review focuses on the molecular mechanisms whereby the transcriptional activation mediated by the interaction between the ARE and NF-E2-related factor 2 (Nrf2) is regulated. Recent studies suggest that the sequence context of the ARE, the nature of the chemical inducers, and the cell type are important for determining the activity of the enhancer in a particular gene.
在暴露于亲电化合物和酚类抗氧化剂的细胞中，编码抗氧化和Ⅱ相解毒酶的基因表达会被诱导。这些酶的诱导在转录水平受到调控，并由位于酶基因启动子中的特定增强子——抗氧化反应元件（ARE）介导。转录因子Nrf2被认为是与ARE相互作用以组成性地或响应氧化应激信号激活基因转录的核心蛋白。本综述聚焦于ARE与NF-E2相关因子2（Nrf2）相互作用介导的转录激活的调控分子机制。最近的研究表明，ARE的序列背景、化学诱导剂的性质以及细胞类型对于确定特定基因中增强子的活性很重要。
