Survival Strategy and Disease Pathogenesis According to the Nrf2‐Small Maf Heterodimer
Survival Strategy and Disease Pathogenesis According to the Nrf2‐Small Maf Heterodimer
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根据 Nrf2-Small Maf 异二聚体的生存策略和疾病发病机制
DOI：
10.1002/9781118148143.ch5
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发表时间：
2011
期刊：
影响因子：
6.7
通讯作者：
H. Motohashi
中科院分区：
文献类型：
--
作者：
Masanobu Morita;H. Motohashi
由于有氧呼吸过程中的氧气消耗以及饮食和/或环境中的外源化学物质，包括哺乳动物在内的生物体不断面临氧化应激。哺乳动物细胞配备了复杂的机制来保护细胞免受氧化和外源应激。 NF-E2 相关因子 2 (Nrf2) 是一种有效的转录激活剂，通过与抗氧化反应元件 (ARE)/亲电子反应元件 (EpRE) 结合，在调节解毒酶和抗氧化蛋白编码基因的表达中发挥核心作用。 Nrf2 是 Cap’n’Collar (CNC) 转录因子家族的成员，该家族通常包含一段独特的氨基酸，称为 CNC 结构域，后面是一个高度保守的碱性区域亮氨酸拉链 (bZIP) 基序。在无应激条件下，Nrf2 被 kelch 样 ECH 相关蛋白 1 (Keap1) 泛素化，并被细胞质中的蛋白酶体降解。当暴露于氧化或外源性应激时，Nrf2 变得稳定，易位到细胞核中，与另一种 bZIP 蛋白小 Maf 异二聚化，与 ARE/EpRE 结合，并激活转录。最近的研究阐明了 Nrf2 响应应激而激活的复杂分子机制，并揭示了 Nrf2 与许多人类疾病有关，包括神经退行性疾病、气道疾病、心血管疾病和癌症。这篇综述涵盖了 Nrf2 发现的历史方面、Nrf2 功能分子研究的最新进展、有关 Nrf2 参与各种病理状况的最新报告以及 Nrf2 利用为人类福利的观点。
Organisms, including mammals, are constantly exposed to oxidative stress due to oxygen consumption during aerobic respiration and xenobiotic chemicals in their diet and/or the environment. Mammalian cells are equipped with sophisticated machinery for cell protection against oxidative and xenobiotic stress. NF-E2-related factor 2 (Nrf2) is a potent transcription activator that plays a central role in regulating the expression of genes encoding detoxifying enzymes and antioxidant proteins by binding to the antioxidant response element (ARE)/electrophile response element (EpRE). Nrf2 is a member of the Cap’n’Collar (CNC) transcription factor family that commonly contains a unique stretch of amino acids, designated the CNC domain, followed by a well-conserved basic region-leucine zipper (bZIP) motif. Under unstressed conditions, Nrf2 is ubiquitinated by kelch-like ECH-associated protein 1 (Keap1) and degraded by the proteasome in the cytoplasm. Upon exposure to oxidative or xenobiotic stress, Nrf2 is stabilized, translocates into the nucleus, heterodimerizes with small Maf, another bZIP protein, binds to the ARE/EpRE, and activates transcription. Recent studies have clarified the intricate molecular mechanisms of Nrf2 activation in response to stress and revealed the involvement of Nrf2 in many human diseases including neurodegeneration, airway disorders, cardiovascular disease, and cancer. This review covers the historical aspects of the discovery of Nrf2, recent advances in molecular studies of Nrf2 function, updated reports on the involvement of Nrf2 in various pathological conditions, and perspectives of Nrf2 utilization for human welfare.
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影响因子：
6
作者：
Lu, ML;Nakamura, RM;Tan, EM
通讯作者：
Tan, EM
影响因子：
10.5
作者：
Itoh, K;Wakabayashi, N;Yamamoto, M
通讯作者：
Yamamoto, M
影响因子：
11.2
作者：
Xu, Changjiang;Huang, Mou-Tuan;Kong, Ah-Ng Tony
通讯作者：
Kong, Ah-Ng Tony
影响因子：
11.2
作者：
Liby, Karen;Royce, Darlene B.;Sporn, Michael B.
通讯作者：
Sporn, Michael B.
DOI：
10.1073/pnas.0403620101
发表时间：
2004-06-29
影响因子：
11.1
作者：
Lee, JM;Chan, KM;Johnson, JA
通讯作者：
Johnson, JA