蛋白磷酸酶2A-C 亚基转录后修饰在细胞氧化应激反应中精细调控的研究

项目名称： 蛋白磷酸酶2A-C 亚基转录后修饰在细胞氧化应激反应中精细调控的研究

项目编号： No.81460506

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 唐深

作者单位： 广西医科大学

项目金额： 50万元

中文摘要： 蛋白磷酸酶2A 是胞内极重要的丝/苏氨酸蛋白磷酸酶，其C亚基羧基端存在T304、Y307两个位点磷酸化和L309位点甲基化的转录后修饰方式。既往基于单一位点单一修饰方式的研究发现PP2A-C转录后修饰可调控PP2A功能，但具体影响方式仍未明了。前期研究提示细胞内PP2A-C存在磷酸化和甲基化组合的双修饰或三修饰状态，在H2O2诱导的PP2A-C甲基丢失过程中不同修饰状态的PP2A-C按一定的先后顺序去甲基，提示氧化应激诱导PP2A-C去甲基有更为精细的调控规律，并与其功能有关。本研究拟以正常人皮肤成纤维细胞为研究对象，综合考虑PP2A-C三个位点及两种修饰方式，研究H2O2对细胞内PP2A-C转录后修饰的精细调控及其对PP2A活性和PP2A结合蛋白的影响。本研究为PP2A依赖的氧化应激相关生物学调控提供依据，为氧化应激介导的相关疾病及化学损伤的防治提供新线索。

中文关键词： 蛋白磷酸酶2A；C；亚基；氧化应激

英文摘要： Protein phosphatase 2A(PP2A) is one of the most important protein serine/threonine phosphatase in mammalian cells. Post-transcriptional modification of PP2A catalytic subunit (PP2A-C) included phosphorylation at T304 and Y307, and methylation at L309. Previous research base on single site and single post-transcriptional modification indicated that post-transcriptional modification plays a crucial role in the regulation of PP2A function, but how it regulates PP2A function is far from clear. Our preliminary studies showed that cellular PP2A-C can be plural modified at T304, Y307 and/or L309 site. Different post-transcriptional modified PP2A-C lost its methyl group according a certain sequence by hydrogen peroxide stimulation. Therefore, we proposed a fine-tuned regulation on PP2A post-transcriptional modification induced by oxidative stress, which is related to its function. In this study, we will investigate how hydrogen peroxide finely regulates PP2A-C post-transcriptional modification in human primary fibroblast cells, and its effect on PP2A activity and PP2A binding protein. This study will provide understanding on oxidative stress induced PP2A dependent biological effect and provide new clue on prevention and treatment of oxidative stress related disease and chemical damage.

英文关键词： Protein phosphatase 2A(PP2A);C subunit;oxidative stress