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定量磷酸化蛋白质组学揭示 GTBP-1 在不同环境温度下调控秀丽隐杆线虫寿命。

Quantitative phosphoproteomics reveals GTBP-1 regulating C.elegans lifespan at different environmental temperatures.

机构信息

State Key Laboratory of Genetic Engineering, Department of Biochemistry, School of Life Sciences, Fudan University, Shanghai, 200438, China.

State Key Laboratory of Genetic Engineering, Department of Biochemistry, School of Life Sciences, Fudan University, Shanghai, 200438, China.

出版信息

Biochem Biophys Res Commun. 2018 Sep 10;503(3):1962-1967. doi: 10.1016/j.bbrc.2018.07.142. Epub 2018 Aug 2.

Abstract

Temperature is one of the primary environmental factors that affect aging, in which protein phosphorylation is an important regulator. Currently, the understanding of phosphorylation events in regulatory networks during aging has remained rather limited. Herein, the phosphoproteomes of C.elegans of different age groups cultured at 20 °C (natural aging) and 25 °C (accelerated aging) were analyzed. Through using the iTRAQ-labeled phosphoproteomics method, 2375 phosphoproteins and 9063 phosphosites were identified. Volcano plots illustrated that 208 proteins during natural aging and 130 proteins during accelerated aging, were significantly changed. Gene ontology and pathway analysis revealed that these proteins were mainly involved in translation, development, metabolisms, and animal behavior processes. Moreover, our results uncovered those kinases CK2, MAPK and CAMK2 might play important roles in aging regulation. Functional experiments confirm that the candidated phosphoprotein GTBP-1 could regulate C.elegans lifespan at 20 °C or 25 °C and is more resistant to heat and oxidative stresses. In summary, our results provided an important resource for future studies of protein phosphorylation in worms. Data are available via ProteomeXchange with identifier PXD009661.

摘要

温度是影响衰老的主要环境因素之一,其中蛋白质磷酸化是一个重要的调节因子。目前,对于衰老过程中调节网络中磷酸化事件的理解仍然相当有限。在此,我们分析了在 20°C(自然衰老)和 25°C(加速衰老)下培养的不同年龄组的秀丽隐杆线虫的磷酸蛋白质组。通过使用 iTRAQ 标记的磷酸蛋白质组学方法,鉴定到 2375 个磷酸化蛋白和 9063 个磷酸化位点。火山图表明,在自然衰老过程中有 208 个蛋白,在加速衰老过程中有 130 个蛋白发生了显著变化。基因本体论和途径分析表明,这些蛋白主要参与翻译、发育、代谢和动物行为过程。此外,我们的结果揭示了 CK2、MAPK 和 CAMK2 等激酶可能在衰老调控中发挥重要作用。功能实验证实候选磷酸蛋白 GTBP-1 可以调节秀丽隐杆线虫在 20°C 或 25°C 的寿命,并且对热和氧化应激更具抗性。总之,我们的研究结果为未来线虫中蛋白质磷酸化的研究提供了重要资源。数据可通过 ProteomeXchange 以标识符 PXD009661 获得。

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