超越 Nrf2 的抑制：Keap1 的最新研究进展。
Beyond repression of Nrf2: An update on Keap1.
机构信息
Department of Medical Biotechnology, Faculty of Biochemistry Biophysics and Biotechnology, Jagiellonian University, 30-387, Krakow, Poland.
Andrus Gerontology Center of the Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, 90089-0191, USA.
出版信息
Free Radic Biol Med. 2020 Sep;157:63-74. doi: 10.1016/j.freeradbiomed.2020.03.023. Epub 2020 Mar 28.
Abstract
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.
摘要
Nrf2（核因子红细胞 2 样 2-NFE2L2）是一种转录因子，通过与一种氧化还原敏感蛋白 Keap1（Kelch 样 ECH 相关蛋白 1）相互作用而受到抑制。Nrf2 转录活性的失调已在多种疾病的发病机制中得到描述，Nrf2/Keap1 轴已成为细胞内稳态的关键调节剂。尽管 Nrf2 在调节生物过程中的意义已得到很好的确立，并在广泛的细节中进行了讨论，但对 Keap1 的关注很少超出对 Nrf2 活性和氧化还原感应的调节。然而，最近的研究和对现有数据的仔细分析表明，Keap1 是细胞功能的一个有趣而有效的调节剂。本综述旨在更深入地了解 Keap1 的结构、相互作用组、调节和非经典功能，从而提高其在细胞生物学中的重要性。我们还旨在强调 Keap1 和 Nrf2 之间的平衡在维持细胞内稳态方面的影响。
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