Production of ribosome components in effector CD4+ T cells is accelerated by TCR stimulation and coordinated by ERK-MAPK

Production of ribosome components in effector CD4+ T cells is accelerated by TCR stimulation and coordinated by ERK-MAPK
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DOI:
10.1016/s1074-7613(03)00268-1
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发表时间:
2003-10-01
期刊:
影响因子:
32.4
通讯作者:
Luban, J
Luban, J
中科院分区:
医学1区
文献类型:
--
作者:
Asmal, M;Colgan, J;Luban, J

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TCR 刺激后效应 CD4(+) T 细胞迅速激活高水平细胞因子表达。与这些细胞中蛋白质生产加速一致,整体 mRNA 谱显示,在细胞因子之后,最令人印象深刻的激活基因簇编码 rRNA 成熟因子。这些基因的激活是ERK-MAPK依赖性的,伴随着rRNA转录的增加和更快的成熟动力学,并且在效应CD4(+) T细胞中比在初始细胞中激活得多。核糖体蛋白亚基 (RPS) 的合成也是 ERK-MAPK 依赖性的,并增加以匹配 rRNA 的产生,但 RPS mRNA 没有明显增加。相反,刺激通过顺式作用的 5'-末端寡嘧啶促进 RPS mRNA 的多核糖体负载。这些结果表明,效应CD4(+) T细胞如何响应细胞外信号协调增加多种核糖体成分以适应迅速增长的细胞因子产生。
Effector CD4(+) T cells rapidly activate high-level cytokine expression following TCR stimulation. Consistent with accelerated protein production in these cells, global mRNA profiles revealed that, after cytokines, the most impressive cluster of activated genes encode rRNA-maturation factors. Activation of these genes was ERK-MAPK dependent, accompanied by increased rRNA transcription and faster maturation kinetics, and much greater in effector CD4(+) T cells than in naive cells. Ribosomal protein subunit (RPS) synthesis was also ERK-MAPK dependent and increased to match rRNA production, but without evident increase in RPS mRNA. Instead, stimulation promoted polysome loading of RPS mRNA via cis-acting, 5'-terminal oligopyrimidines. These results demonstrate how, in response to extracellular signals, effector CD4(+) T cells coordinately increase multiple ribosomal components to accommodate burgeoning cytokine production.