Arginine methylation of SKN-1 promotes oxidative stress resistance in Caenorhabditis elegans
Arginine methylation of SKN-1 promotes oxidative stress resistance in Caenorhabditis elegans
复制标题
SKN-1的精氨酸甲基化促进秀丽隐杆线虫的氧化应激抵抗
DOI：
10.1016/j.redox.2019.101111
复制
发表时间：
2019-02-01
期刊：
影响因子：
11.4
通讯作者：
Li, Xiaoxue
中科院分区：
文献类型：
--
作者：
Li, Hongyuan;Su, Liangping;Li, Xiaoxue
秀丽隐杆线虫NRF(核因子-E_2相关因子)/Cn(Capn‘n’项圈)转录因子Skinhead-1(SKN-1)在促进氧化应激诱导的II期解毒基因表达中起着保守的关键作用。SKN-1的活性受众所周知的磷酸化和最近报道的O-GlcN酰化的控制。SKN-1是否存在其他类型的翻译后修饰并影响其功能仍不清楚。在这里，我们发现SKN-1的精氨酸484和516(R484/R516)被PRMT-1不对称地甲基化。氧化应激增强了PRMT-1与SKN-1的结合。因此，SKN-1上精氨酸的不对称二甲基化水平升高。PrMT-1的缺失或R484/R516二甲基化的中断减少了SKN1在SKN-1驱动的第二相解毒基因启动子上的浓缩，这些启动子包括γ-谷氨酰胺半胱氨酸合成酶GcS-1、谷胱甘肽S转移酶Gst-7和Gst-4，从而降低了蠕虫抵御氧化应激的能力。这些发现对于研究精氨酸甲基化在人类氧化应激反应相关疾病中保守的NRF/CnC转录因子上的生理和病理功能具有重要意义。
Caenorhabditis elegans NRF (NF-E2-related factor)/CNC (Cap'n'collar) transcription factor, Skinhead-1 (SKN-1), is conservatively critical for promoting phase II detoxification gene expressions in response to oxidative stress. SKN-1 activity is controlled by well-known phosphorylation and recently-reported O-GlcNAcylation. Whether other kinds of posttanslational modifications of SKN-1 occur and influence its function remains elusive. Here, we found arginines 484 and 516 (R484/R516) of SKN-1 were asymmetrically dimethylated by PRMT-1. Oxidative stress enhanced the binding of PRMT-1 to SKN-1. Consequently, asymmetrical dimethylation of arginines on SKN-1 was elevated. Loss of prmt-1 or disruption of R484/R516 dimethylation decreased the enrichment of SKN1 on the promoters of SKN-1-driven phase II detoxification genes, including gamma-glutamine cysteine synthetase gcs-1, glutathione S-transferases gst-7 and gst-4, which resulted in reduced ability of worms to defense against oxidative stress. These findings have important implications for investigating the physiological and pathological functions of arginine methylation on conserved NRF/CNC transcription factors in human diseases related to oxidative stress response.