Epigenetic regulation of Keap1-Nrf2 signaling.
Epigenetic regulation of Keap1-Nrf2 signaling.
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DOI：
10.1016/j.freeradbiomed.2015.06.013
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发表时间：
2015-11
影响因子：
7.4
通讯作者：
Kong AN
中科院分区：
文献类型：
--
作者：
Guo Y;Yu S;Zhang C;Kong AN
Kelch样ECH相关蛋白1（Keap 1）-核因子红细胞2相关因子2（Nrf 2）信号传导轴作为一个“主调节器”，通过协调诱导广泛的细胞保护基因来响应氧化/亲电应激和化学损伤。因此，Nrf 2的激活被认为是预防由压力和毒素引发的慢性疾病（包括癌症）的重要方法。尽管广泛的研究表明Keap 1-Nrf 2信号通路在转录、翻译和翻译后水平上受到多层调控，但Nrf 2和Keap 1的潜在表观遗传调控只是在最近几年才开始被认识到。表观遗传修饰，基因表达的遗传改变，发生在没有改变的主要DNA序列，已被报道深刻参与氧化应激反应。在这篇综述中，我们讨论了最新的研究结果关于表观遗传调控的Keap 1-Nrf 2信号的DNA甲基化，组蛋白修饰，和microRNA。这些表观遗传修饰的调节Keap 1-Nrf 2信号通路之间的串扰也进行了讨论。对Nrf 2和Keap 1表观遗传修饰的研究不仅增强了我们对这一复杂细胞防御系统的理解，而且为预防某些疾病提供了潜在的新治疗靶点。
The kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) signaling axis serves as a “master regulator” in response to oxidative/electrophilic stresses and chemical insults through the coordinated induction of a wide array of cytoprotective genes. Therefore, activation of Nrf2 is considered to be an important approach for preventing chronic diseases triggered by stresses and toxins, including cancer. Despite extensive studies suggested that the Keap1-Nrf2 signaling pathway is subject to multiple layers of regulation at the transcriptional, translational, and post-translational levels, the potential epigenetic regulation of Nrf2 and Keap1 has begun to be recognized only in recent years. Epigenetic modifications, heritable alterations in gene expression that occur without changes in the primary DNA sequence, have been reported to be profoundly involved in oxidative stress responses. In this review, we discuss the latest findings regarding the epigenetic regulation of Keap1-Nrf2 signaling by DNA methylation, histone modification, and microRNAs. The crosstalk among these epigenetic modifications in the regulation of Keap1-Nrf2 signaling pathways is also discussed. Studies of the epigenetic modification of Nrf2 and Keap1 have not only enhanced our understanding of this complex cellular defense system but have also provided potential new therapeutic targets for the prevention of certain diseases.