a School of Preclinical Medicine , Guangxi Medical University , Nanning , People's Republic of China.
b School of Public Health, Guangxi Medical University , Nanning , People's Republic of China.
Redox Rep. 2019 Dec;24(1):1-9. doi: 10.1080/13510002.2019.1595332.
Protein phosphatase 2A (PP2A), a major serine/threonine phosphatase, is also known to be a target of ROS. The methylation of PP2A can be catalyzed by leucine carboxyl methyltransferase-1 (LCMT1), which regulates PP2A activity and substrate specificity.
In the previous study, we have showed that LCMT1-dependent PP2Ac methylation arrests HO-induced cell oxidative stress damage. To explore the possible protective mechanism, we performed iTRAQ-based comparative quantitative proteomics and phosphoproteomics studies of HO-treated vector control and LCMT1-overexpressing cells.
A total of 4480 non-redundant proteins and 3801 unique phosphopeptides were identified by this means. By comparing the HO-regulated proteins in LCMT1-overexpressing and vector control cells, we found that these differences were mainly related to protein phosphorylation, gene expression, protein maturation, the cytoskeleton and cell division. Further investigation of LCMT1 overexpression-specific regulated proteins under HO treatment supported the idea that LCMT1 overexpression induced ageneral dephosphorylation of proteins and indicated increased expression of non-erythrocytic hemoglobin, inactivation of MAPK3 and regulation of proteins related to Rho signal transduction, which were known to be linked to the regulation of the cytoskeleton.
These data provide proteomics and phosphoproteomics insights into the association of LCMT1-dependent PP2Ac methylation and oxidative stress and indirectly indicate that the methylation of PP2A plays an important role against oxidative stress.
蛋白磷酸酶 2A（PP2A）是一种主要的丝氨酸/苏氨酸磷酸酶，也是活性氧（ROS）的靶点。PP2A 的甲基化可以被亮氨酸羧基甲基转移酶-1（LCMT1）催化，后者调节 PP2A 的活性和底物特异性。
在之前的研究中，我们已经表明，LCMT1 依赖性 PP2Ac 甲基化可阻止 HO 诱导的细胞氧化应激损伤。为了探讨可能的保护机制，我们对 HO 处理的对照载体和 LCMT1 过表达细胞进行了基于 iTRAQ 的比较定量蛋白质组学和磷酸蛋白质组学研究。
通过这种方法共鉴定到 4480 个非冗余蛋白和 3801 个独特的磷酸肽。通过比较 LCMT1 过表达和对照载体细胞中 HO 调节的蛋白质，我们发现这些差异主要与蛋白质磷酸化、基因表达、蛋白质成熟、细胞骨架和细胞分裂有关。进一步研究 HO 处理下 LCMT1 过表达特异性调节的蛋白质支持了 LCMT1 过表达诱导蛋白质普遍去磷酸化的观点，并表明非红细胞血红蛋白表达增加、MAPK3 失活以及与 Rho 信号转导调节相关的蛋白质调节，这些都与细胞骨架的调节有关。
这些数据为 LCMT1 依赖性 PP2Ac 甲基化与氧化应激的关联提供了蛋白质组学和磷酸蛋白质组学的见解，并间接表明 PP2A 的甲基化在抵抗氧化应激中起着重要作用。
