Profiling of Protein O-GlcNAcylation in Murine CD8(+) Effector- and Memory-like T Cells.
Profiling of Protein O-GlcNAcylation in Murine CD8(+) Effector- and Memory-like T Cells.
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DOI：
10.1021/acschembio.7b00869
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发表时间：
2017-12-15
影响因子：
4
通讯作者：
Wu P
中科院分区：
文献类型：
--
作者：
Lopez Aguilar A;Gao Y;Hou X;Lauvau G;Yates JR;Wu P
在急性感染期间，抗原刺激导致初始 CD8 + T 细胞激活、扩增和分化，首先分化为细胞毒性效应细胞，最终分化为长寿命记忆细胞。 T 细胞抗原受体 (TCR) 以与主要组织相容性复合体 I (MHC-I) 编码分子结合的抗原肽的形式检测抗原呈递细胞 (APC) 上的抗原，并启动 TCR 信号转导网络。该过程由许多细胞内信号蛋白的磷酸化介导。蛋白质 O-GlcNAc 修饰是该过程中涉及的另一种翻译后修饰，通常与磷酸化具有相互作用或协同作用。在这项研究中，我们利用化学酶聚糖标记技术和蛋白质组学分析，比较了体外分化的小鼠效应子和记忆样CD8+ T细胞的蛋白质O-GlcNAcNAc化。通过定量蛋白质组学分析，我们鉴定了 445 种蛋白质，它们在效应样 T 细胞亚群或记忆样 T 细胞亚群中受到显着调节。此外，定性和定量分析发现了高度调控的蛋白质簇，表明这种翻译后修饰参与了特定的细胞过程。在效应样 T 细胞中，蛋白 O-GlcNAc 酰化大量参与驱动效应 T 细胞快速增殖的转录和翻译过程。在记忆样 T 细胞的形成过程中，蛋白质 O-GlcNAc 酰化参与了转录、mRNA 加工和翻译的更特异、或许更有针对性的调节。值得注意的是，O-GlcNAc 作为两个 CD8+ T 细胞亚群中“组蛋白密码”的一部分发挥着关键作用。
During an acute infection, antigenic stimulation leads to activation, expansion, and differentiation of naïve CD8 + T cells, first into cytotoxic effector cells and eventually into long-lived memory cells. T cell antigen receptors (TCRs) detect antigens on antigen-presenting cells (APCs) in the form of antigenic peptides bound to major histocompatibility complex I (MHC-I)-encoded molecules and initiate TCR signal transduction network. This process is mediated by phosphorylation of many intracellular signaling proteins. Protein O-GlcNAc modification is another post-translational modification involved in this process, which often has either reciprocal or synergistic roles with phosphorylation. In this study, using a chemoenzymatic glycan labeling technique and proteomics analysis, we compared protein O-GlcNAcylation of murine effector and memory-like CD8+ T cells differentiated in vitro. By quantitative proteomics analysis, we identified 445 proteins that are significantly regulated in either effector- or memory-like T cell subsets. Furthermore, qualitative and quantitative analysis identified highly regulated protein clusters that suggest involvement of this post-translational modification in specific cellular processes. In effector-like T cells, protein O-GlcNAcylation is heavily involved in transcriptional and translational processes that drive fast effector T cells proliferation. During the formation of memory-like T cells, protein O-GlcNAcylation is involved in a more specific, perhaps more targeted regulation of transcription, mRNA processing, and translation. Significantly, O-GlcNAc plays a critical role as part of the “histone code” in both CD8+ T cells subgroups.
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影响因子：
14.8
作者：
Guo, Min;Schimmel, Paul
通讯作者：
Schimmel, Paul
DOI：
10.1083/jcb.201501101
发表时间：
2015-03-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
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通讯作者：
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DOI：
10.1073/pnas.1013822108
发表时间：
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影响因子：
11.1
作者：
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通讯作者：
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影响因子：
16.8
作者：
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通讯作者：
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影响因子：
30.5
作者：
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通讯作者：
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