Hydrogen peroxide redistributes the localization of protein phosphatase methylesterase 1
Hydrogen peroxide redistributes the localization of protein phosphatase methylesterase 1
复制标题
过氧化氢重新分配蛋白磷酸酶甲酯酶 1 的定位
DOI：
10.1016/j.lfs.2018.10.029
复制
发表时间：
2018
期刊：
影响因子：
6.1
通讯作者：
Li Xiyi
中科院分区：
文献类型：
--
作者：
Tang Shen;Lu Cailing;Mo Laiming;Wang Xinhang;Liang Ziwei;Qin Fu;Liu Yinpin;Liu Yuyang;Huang Haiyan;Huang Yue;Cai Haiqing;Xiao Deqiang;Guo Songchao;Ouyang Yiqiang;Sun Bin;Li Xiyi
AimsProtein phosphatase methylesterase-1 (PME-1) is a serine hydrolase that catalyzes protein phosphatase 2A (PP2A) demethylation and negatively regulates its activity. PME-1 is compartmentalized within cells to precisely control the demethylation of PP2A. This study investigated the localization of PME-1 in human fibroblast cells (HDF) under oxidative stress.Main methodsAlkaline demethylation and peptide competition assays were applied to detect the methylation sensitivity of anti-PP2Ac. The localization of PME-1, leucine carboxyl methyltransferase 1 (LCMT1), demethylated-phosphorylated-PP2Ac (dem-p-PP2Ac) and total PP2Ac was determined by immunofluorescence analysis, and protein expression was measured by Western blot. A HEK293 cell line stably expressing constructed PME-1-EGFP was used to dynamically monitor the nuclear export of PME-1 under oxidative stress.Key resultsAfter hydrogen peroxide (H2O2) treatment, the protein expression of PME-1 remained unchanged, while PME-1 facilitated redistribution from the nucleus to the cytoplasm in HDF according to immunofluorescence analysis. In constructed HEK293 cells, the EGFP-tagged PME-1 was exported from the nucleus to the cytoplasm after H2O2treatment, and nuclear export was eliminated after leptomycin B additions. Our observation of dem-p-PP2Ac species relocation from the nucleus to the cytoplasm under oxidative stress is consistent with the redistribution patterns of PME-1. AntioxidantN-acetyl cysteine can reverse the nuclear to cytoplasmic ratio of PME-1 proteins and dem-p-PP2Ac after H2O2exposure.SignificanceWe found that PME-1 is exported from the nucleus to the cytoplasm upon H2O2treatment and redistributes dem-p-PP2Ac in subcellular compartments. These findings offer new insight into the regulation of PME-1 localization and PP2A demethylation under oxidative stress.
