Beyond repression of Nrf2: An update on Keap1.

Beyond repression of Nrf2: An update on Keap1.
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DOI:
10.1016/j.freeradbiomed.2020.03.023
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发表时间:
2020-09
影响因子:
7.4
通讯作者:
Grochot-Przeczek A
Grochot-Przeczek A
中科院分区:
医学1区
文献类型:
--
作者:
Kopacz A;Kloska D;Forman HJ;Jozkowicz A;Grochot-Przeczek A

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Nrf 2(NFE 2L 2- nuclear factor(erythoid-derived 2)-like 2)是一种转录因子,通过与氧化还原敏感蛋白Keap 1(Kelch-like ECH-associated protein 1)相互作用而被抑制。在多种疾病的发病机制中已经描述了Nrf 2转录活性的失调,并且Nrf 2/Keap 1轴已经成为细胞稳态的重要调节剂。虽然Nrf 2在生物过程调节中的重要性已经得到了很好的确立和广泛的详细讨论,但对Keap 1的关注很少超出Nrf 2活性和氧化还原传感的调节。然而,最近的研究和对现有数据的仔细分析表明,Keap 1是一种有趣且有效的细胞功能调节剂。本文就Keap 1的结构、相互作用组、调控和非经典功能等方面的研究进展作一综述,以进一步阐明Keap 1在细胞生物学中的重要意义。我们还打算强调Keap 1和Nrf 2之间的平衡对维持细胞内稳态的影响。
Nrf2 (NFE2L2 – nuclear factor (erythroid-derived 2)-like 2) is a transcription factor, which is repressed by interaction with a redox-sensitive protein Keap1 (Kelch-like ECH-associated protein 1). Deregulation of Nrf2 transcriptional activity has been described in the pathogenesis of multiple diseases, and the Nrf2/Keap1 axis has emerged as a crucial modulator of cellular homeostasis. Whereas the significance of Nrf2 in the modulation of biological processes has been well established and broadly discussed in detail, the focus on Keap1 rarely goes beyond the regulation of Nrf2 activity and redox sensing. However, recent studies and scrutinized analysis of available data point to Keap1 as an intriguing and potent regulator of cellular function. This review aims to shed more light on Keap1 structure, interactome, regulation and non-canonical functions, thereby enhancing its significance in cell biology. We also intend to highlight the impact of balance between Keap1 and Nrf2 in the maintenance of cellular homeostasis.
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