Methylation of arginine by PRMT1 regulates Nrf2 transcriptional activity during the antioxidative response
Methylation of arginine by PRMT1 regulates Nrf2 transcriptional activity during the antioxidative response
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PRMT1 对精氨酸的甲基化调节抗氧化反应过程中 Nrf2 转录活性
DOI：
10.1016/j.bbamcr.2016.05.009
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发表时间：
2016-08-01
影响因子：
5.1
通讯作者：
Lu, Jun
中科院分区：
文献类型：
--
作者：
Liu, Xin;Li, Hongyuan;Lu, Jun
帽领转录因子家族在抗氧化性和亲电性胁迫中发挥着重要作用。在CnC家族成员中，核因子-E2相关因子2(NRF2)是通过抗氧化剂反应元件(ARE)介导的反式激活调节抗氧化剂和II相酶的关键。Nrf2的活性受多种翻译后修饰的控制，包括磷酸化、泛素化、乙酰化和苏莫化。在这里，我们证明了在体外和体内，精氨酸甲基转移酶-1(PRMT1)在精氨酸437的单一残基上甲基化Nrf2蛋白。以血红素加氧酶-1(HO-1)作为II相酶基因的模型，我们发现PRMT1甲基化Nrf2导致其DNA结合活性和反式激活适度增加，从而保护细胞免受tBHP诱导的谷胱甘肽耗竭和细胞死亡。总的来说，我们的结果定义了Nrf2的一种新的修饰，它作为一种微调机制来调节Nrf2在氧化应激下的转录活性。(C)2016爱思唯尔B.V.保留所有权利。
The cap collar (CNC) family of transcription factors play important roles in resistance of oxidative and electrophilic stresses. Among the CNC family members, NF-E2-related factor 2 (Nrf2) is critical for regulating the antioxidant and phase II enzymes through antioxidant response element (ARE)-mediated transactivation. The activity of Nrf2 is controlled by a variety of post-translational modifications, including phosphorylation, ubiquitination, acetylation and sumoylation. Here we demonstrate that the arginine methyltransferase-1 (PRMT1) methylates Nrf2 protein at a single residue of arginine 437, both in vitro and in vivo. Using the heme oxygenase-1 (HO-1) as a model of phase II enzyme gene, we found that methylation of Nrf2 by PRMT1 led to a moderate increase of its DNA-binding activity and transactivation, which subsequently protected cells against the tBHP-induced glutathione depletion and cell death. Collectively, our results define a novel modification of Nrf2, which operates as a fine-tuning mechanism for the transcriptional activity of Nrf2 under the oxidative stress. (C) 2016 Elsevier B.V. All rights reserved.