CtBP2 confers protection against oxidative stress through interactions with NRF1 and NRF2
CtBP2 confers protection against oxidative stress through interactions with NRF1 and NRF2
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DOI：
10.1016/j.bbrc.2021.05.069
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发表时间：
2021-05-27
影响因子：
3.1
通讯作者：
Shimano, Hitoshi
中科院分区：
文献类型：
--
作者：
Kainoh, Kenta;Takano, Ryo;Shimano, Hitoshi
虽然分子氧对于需氧生物体是必不可少的，但其利用与氧化损伤的产生不可分割地联系在一起。为了科普有害的方面，细胞进化出抗氧化防御系统，并且氧化损伤的管理不足是多种疾病的发病机制的基础。这种抗氧化防御的一系列基因受转录因子核因子红细胞2样1和2（NRF 1和NRF 2）的调控。虽然已经研究了NRF激活的调节步骤，特别强调核转位和蛋白体降解，考虑到这些防御系统不可或缺的性质，可能存在未知的冗余。在这里，我们揭示了C-末端结合蛋白2（CtBP 2），一个具有氧化还原敏感能力的转录辅因子，是NRFs的一个专性伴侣。CtBP 2与NRF 1和NRF 2形成转录复合物，这是促进抗氧化基因响应氧化损伤的表达所必需的。我们的研究结果说明了一个基础，了解转录调控的抗氧化防御系统，可以利用治疗。(c)2021爱思唯尔公司All rights reserved.
While molecular oxygen is essential for aerobic organisms, its utilization is inseparably connected with generation of oxidative insults. To cope with the detrimental aspects, cells evolved antioxidative defense systems, and insufficient management of the oxidative insults underlies the pathogenesis of a wide range of diseases. A battery of genes for this antioxidative defense are regulated by the transcription factors nuclear factor-erythroid 2-like 1 and 2 (NRF1 and NRF2). While the regulatory steps for the activation of NRFs have been investigated with particular emphasis on nuclear translocation and proteosomal degradation, unknown redundancy may exist considering the indispensable nature of these defense systems. Here we unraveled that C-terminal binding protein 2 (CtBP2), a transcriptional cofactor with redox-sensing capability, is an obligate partner of NRFs. CtBP2 forms transcriptional complexes with NRF1 and NRF2 that is required to promote the expression of antioxidant genes in response to oxidative insults. Our findings illustrate a basis for understanding the transcriptional regulation of antioxidative defense systems that may be exploited therapeutically. (c) 2021 Elsevier Inc. All rights reserved.