Quantitative analysis of how Myc controls T cell proteomes and metabolic pathways during T cell activation
Quantitative analysis of how Myc controls T cell proteomes and metabolic pathways during T cell activation
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DOI：
10.7554/elife.53725
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发表时间：
2020-02-05
期刊：
影响因子：
7.7
通讯作者：
Cantrell, Doreen A.
中科院分区：
文献类型：
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作者：
Marchingo, Julia M.;Sinclair, Linda, V;Cantrell, Doreen A.
T细胞的扩增和分化严重依赖于转录因子c-Myc（Myc）。在此，我们使用定量质谱来揭示Myc如何控制抗原受体驱动的细胞生长和蛋白质组重构小鼠T细胞。对每个细胞中>7000种蛋白质的拷贝数的分析提供了对Myc在控制控制T细胞命运的蛋白质机制中的选择性作用的新理解。这些数据鉴定了免疫活化T细胞中Myc依赖性和独立性代谢过程。我们发现Myc的主要功能是控制多个氨基酸转运蛋白的表达，并且单个Myc控制的氨基酸转运蛋白的丢失有效地表型化Myc缺失的影响。这项研究提供了Myc如何选择性地塑造T细胞表型的综合图谱，揭示了Myc诱导氨基酸转运对于随后的生物能量和生物合成程序至关重要，并许可T细胞受体驱动的蛋白质组重编程。
T cell expansion and differentiation are critically dependent on the transcription factor c-Myc (Myc). Herein we use quantitative mass-spectrometry to reveal how Myc controls antigen receptor driven cell growth and proteome restructuring in murine T cells. Analysis of copy numbers per cell of >7000 proteins provides new understanding of the selective role of Myc in controlling the protein machinery that govern T cell fate. The data identify both Myc dependent and independent metabolic processes in immune activated T cells. We uncover that a primary function of Myc is to control expression of multiple amino acid transporters and that loss of a single Myc-controlled amino acid transporter effectively phenocopies the impact of Myc deletion. This study provides a comprehensive map of how Myc selectively shapes T cell phenotypes, revealing that Myc induction of amino acid transport is pivotal for subsequent bioenergetic and biosynthetic programs and licences T cell receptor driven proteome reprogramming.