定量蛋白质组学揭示O-GlcNAc修饰稳定其底物蛋白
详细信息 查看官网全文
- 英文论文题名：Quantitative chemoproteomic profiling of O-GlcNAc dynamics reveals its role in regulating protein stability
- 论文作者：秦为 ; 陈影 ; 全柏峄 ; 吕品欧 ; 陈兴 ; 王初
- 英文论文作者：Wei Qin ; Ying Chen ; BaiyiQuan ; Pinou Lv ; Xing Chen ; Chu Wang ; Peking-Tsinghua Center for Life Science ; Peking University ; Department of Chemistry ; Peking University
- 年：2016
- 作者机构：北京大学-清华大学生命科学联合中心,北京大学;北京大学化学与分子工程学院北京大学;
- 论文关键词：O-GlcNAc ; 定量蛋白质组学 ; 蛋白稳定性
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第二十八分会：化学生物学
- 语种：中文
- 分类号：Q51
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第二十八分会 ; 化学生物学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：132k
- 原文格式：D
- 会议级别：全国
摘要
O-GlcNAc是一种生物体内非常重要的蛋白翻译后修饰,广泛参与到细胞内不同的信号通路中。细胞内O-GlcNAc修饰水平由OGT和OGA精密调控,因此O-GlcNAc是一种高度动态的翻译后修饰。通过蛋白质组学手段定量地分析O-GlcNAc修饰的动态变化对研究其生物学功能有着重要意义。本课题中,我们结合了现有的SILAC和非天然糖代谢标记的方法,建立了定量分析O-GlcNAc蛋白动态变化的化学蛋白质组学平台。通过这个平台,我们大规模定量地鉴定了大约1000个O-GlcNAc修饰的蛋白,极大地扩充了文献报道的O-GlcNAc修饰蛋白库。利用非天然糖Pulse-chase的策略,我们区分了具有稳定修饰的0-GlcNAc蛋白以及相对动态的O-GlcNAc的蛋白。我们进一步发现稳定修饰的O-GlcNAc调控其底物蛋白的稳定性,降低O-GlcNAc水平可以观察到稳定的0-GlcNAc蛋白更容易发生降解。
It is very important to quantitatively detect the dynamics of O-GlcNAcylation by proteomic study for better understanding the biological roles of O-GlcNAcylation in cellular processes.Traditional proteomic study often read out the change of O-GlcNAcylation level between two samples.Systemic study of the O-GlcNAcylated dynamics on proteins remains challenging.Here we combined the stable isotope amino acids labeling in cell culture(SILAC)and specific O-GlcNAcylated chemical reporters to quantitatively identify over 1000 O-GlcNAcylated proteins.We were able to distinguish the relative stable or dynamic O-GlcNAcylated proteins,from which we discovered ~100 proteins with relative slow dynamics of O-GlcNAcylation.We provided further evidence that these stable O-GlcNAcylation regulate the stability and function of their modified substrates.
It is very important to quantitatively detect the dynamics of O-GlcNAcylation by proteomic study for better understanding the biological roles of O-GlcNAcylation in cellular processes.Traditional proteomic study often read out the change of O-GlcNAcylation level between two samples.Systemic study of the O-GlcNAcylated dynamics on proteins remains challenging.Here we combined the stable isotope amino acids labeling in cell culture(SILAC)and specific O-GlcNAcylated chemical reporters to quantitatively identify over 1000 O-GlcNAcylated proteins.We were able to distinguish the relative stable or dynamic O-GlcNAcylated proteins,from which we discovered ~100 proteins with relative slow dynamics of O-GlcNAcylation.We provided further evidence that these stable O-GlcNAcylation regulate the stability and function of their modified substrates.
引文