Proteomics and phosphoproteomics study of LCMT1 overexpression and oxidative stress: overexpression of LCMT1 arrests H2O2-induced lose of cells viability

Proteomics and phosphoproteomics study of LCMT1 overexpression and oxidative stress: overexpression of LCMT1 arrests H2O2-induced lose of cells viability
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LCMT1 过度表达和氧化应激的蛋白质组学和磷酸蛋白质组学研究:LCMT1 过度表达阻止 H2O2 诱导的细胞活力丧失

DOI:
10.1080/13510002.2019.1595332
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发表时间:
2019-01
期刊:
影响因子:
3.8
通讯作者:
Li Xiyi
Li Xiyi
中科院分区:
生物学3区
文献类型:
--
作者:
Wang Xinhang;Tang Shen;Qin Fu;Liu Yuyang;Liang Ziwei;Cai Haiqing;Mo Laiming;Xiao Deqiang;Guo Songcao;Ouyang Yiqiang;Sun Bin;Lu Cailing;Li Xiyi

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摘要目的:蛋白磷酸酶2A(PP 2A),一种主要的丝氨酸/苏氨酸磷酸酶,也是已知的ROS的靶点。亮氨酸羧基甲基转移酶1(Leucine Carboxy Methyltransferase-1,LCMT 1)可催化PP 2A的甲基化,并调节PP 2A的活性和底物特异性。方法:在先前的研究中,我们已经表明LCMT 1依赖的PP 2Ac甲基化阻止H2 O2诱导的细胞氧化应激损伤。为了探索可能的保护机制,我们进行了基于iTRAQ的比较定量蛋白质组学和磷酸化蛋白质组学研究H2 O2处理的载体对照和LCMT 1过表达细胞。结果:共鉴定出4480个非冗余蛋白和3801个独特的磷酸肽。通过比较LCMT 1过表达细胞和载体对照细胞中H2 O2调节蛋白的差异,发现这些差异主要与蛋白磷酸化、基因表达、蛋白成熟、细胞骨架和细胞分裂有关。进一步研究LCMT 1过表达特异性调节蛋白在H2 O2处理下支持LCMT 1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,MAPK 3失活和Rho信号转导相关蛋白的调节,已知这些蛋白与细胞骨架的调节有关。讨论内容:这些数据提供了蛋白质组学和磷酸化蛋白质组学的见解LCMT 1依赖的PP 2Ac甲基化和氧化应激的关联,并间接表明PP 2A的甲基化在抗氧化应激中起着重要作用。
ABSTRACT Objectives: 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. Methods: In the previous study, we have showed that LCMT1-dependent PP2Ac methylation arrests H2O2-induced cell oxidative stress damage. To explore the possible protective mechanism, we performed iTRAQ-based comparative quantitative proteomics and phosphoproteomics studies of H2O2-treated vector control and LCMT1-overexpressing cells. Results: A total of 4480 non-redundant proteins and 3801 unique phosphopeptides were identified by this means. By comparing the H2O2-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 H2O2 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. Discussion: 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.
DOI: 10.1038/srep43161
发表时间: 2017-02-22
期刊: Scientific reports
影响因子: 4.6
作者:
Peng X;Yan T;Sun M
通讯作者: Sun M
DOI: --
发表时间: 2010-04
期刊: Journal of physiology and pharmacology : an official journal of the Polish Physiological Society
影响因子: --
作者:
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通讯作者: B. Budziszewska;Magdalena Szymanska;M. Leśkiewicz;A. Basta-Kaim;L. Jaworska-Feil;M. Kubera;D. Jantas;W. Lasoń
DOI: 10.1073/pnas.0813216106
发表时间: 2009-09-08
影响因子: 11.1
作者:
Biagioli, Marta;Pinto, Milena;Gustincich, Stefano
通讯作者: Gustincich, Stefano
DOI: 10.1016/j.cub.2013.11.048
发表时间: 2014-01-20
期刊: CURRENT BIOLOGY
影响因子: 9.2
作者:
Abreu-Blanco, Maria Teresa;Verboon, Jeffrey M.;Parkhurst, Susan M.
通讯作者: Parkhurst, Susan M.
DOI: 10.1152/ajpheart.01050.2003
发表时间: 2004-06-01
影响因子: 4.8
作者:
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通讯作者: Hofmann, PA