An important role of Nrf2-ARE pathway in the cellular defense mechanism.
An important role of Nrf2-ARE pathway in the cellular defense mechanism.
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DOI：
10.5483/bmbrep.2004.37.2.139
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发表时间：
2004-03
期刊：
影响因子：
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通讯作者：
Jong‐Min Lee;Jeffrey A. Johnson
中科院分区：
文献类型：
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作者：
Jong‐Min Lee;Jeffrey A. Johnson
抗氧化应答元件（ARE）是编码II期解毒酶和抗氧化蛋白的顺式调控元件，如NAD(P)H：醌氧化还原酶1、谷胱甘肽s-转移酶和谷氨酸-半胱氨酸连接酶。有趣的是，据报道，Nrf2 （nf - e2相关因子2）在各种细胞类型中调控大量的are驱动基因。Nrf2是一种碱性亮氨酸拉链转录因子，最初被鉴定为β -珠蛋白基因位点控制区的结合蛋白。Nrf2的DNA结合序列与ARE序列非常相似，许多研究表明Nrf2结合ARE位点导致下游基因上调。Nrf2及其下游靶基因的功能提示Nrf2- are通路在细胞抗氧化防御系统中起重要作用。为了支持这一点，许多研究表明Nrf2在细胞保护和抗癌中起关键作用，这意味着Nrf2- are途径可能作为神经退行性疾病和癌症的治疗靶点，其中氧化应激密切相关。
The antioxidant responsive element (ARE) is a cis-acting regulatory element of genes encoding phase II detoxification enzymes and antioxidant proteins, such as NAD(P)H: quinone oxidoreductase 1, glutathione S-transferases, and glutamate-cysteine ligase. Interestingly, it has been reported that Nrf2 (NF-E2-related factor 2) regulates a wide array of ARE-driven genes in various cell types. Nrf2 is a basic leucine zipper transcription factor, which was originally identified as a binding protein of locus control region of beta-globin gene. The DNA binding sequence of Nrf2 and ARE sequence are very similar, and many studies demonstrated that Nrf2 binds to the ARE sites leading to up-regulation of downstream genes. The function of Nrf2 and its downstream target genes suggests that the Nrf2-ARE pathway is important in the cellular antioxidant defense system. In support of this, many studies showed a critical role of Nrf2 in cellular protection and anti-carcinogenicity, implying that the Nrf2-ARE pathway may serve as a therapeutic target for neurodegenerative diseases and cancers, in which oxidative stress is closely implicated.