Regulation of interleukin 2 gene expression by CD28 costimulation in mouse T-cell clones: both nuclear and cytoplasmic RNAs are regulated with complex kinetics
Regulation of interleukin 2 gene expression by CD28 costimulation in mouse T-cell clones: both nuclear and cytoplasmic RNAs are regulated with complex kinetics
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小鼠 T 细胞克隆中 CD28 共刺激对白细胞介素 2 基因表达的调节：核和细胞质 RNA 均受到复杂动力学的调节
DOI：
10.1128/mcb.15.6.3197
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发表时间：
1995
影响因子：
5.3
通讯作者：
Ronald H. Schwartz
中科院分区：
文献类型：
--
作者：
Scott W. Umlauf;B. Beverly;Olivier Lantz;Ronald H. Schwartz
T 细胞受体 (TCR) 信号传导是诱导小鼠 T 细胞中白细胞介素 2 (IL-2) 基因表达所必需的。通过 CD28 进行的额外共刺激可使 IL-2 的产生增加 30 至 100 倍。使用 IL-2 RNA 积累和转录报告基因测定，我们已经解决了不同刺激时间点 CD28 调节的潜在机制。 TCR 和 CD28 信号对 IL-2 mRNA 的动力学调节是复杂的：（i）在最早可检测的时间点，CD28 信号传导导致与单独的 TCR 信号传导相比增加 20 倍； (ii) 两组均在前 4 小时内快速积累 mRNA； (iii) IL-2 mRNA随后从仅通过TCR刺激的细胞中消失，但在通过CD28共刺激的细胞中趋于平稳或略有增加； (iv) 8小时后，mRNA在含有抗CD28抗体的培养物中消失。转录报告基因检测未显示 CD28 信号传导对 IL-2 增强子驱动的转录的特定影响。对于 353-kb 或 1.9-kb 增强子来说，在广泛的动力学和 TCR 占有率以及多种 TCR 信号模拟物中都是如此。然而，CD28 共刺激的早期成分是细胞核，因为 mRNA 的初始增强也存在于未剪接的 IL-2 RNA 中。 2 到 6 小时之间，在存在和不存在 CD28 信号传导的情况下，IL-2 mRNA 的衰减率存在显着差异。即使在存在 CD28 信号的情况下，IL-2 mRNA 在 8 小时后也开始快速衰减，尽管衰减发生的速度比单独抗 TCR 刺激 4 小时后观察到的速度慢。这种复杂性表明存在两种有趣的分子机制，CD28 通过这些机制共刺激淋巴因子基因表达。
T-cell receptor (TCR) signalling is required to induce expression of the interleukin 2 (IL-2) gene in mouse T cells. Additional costimulation through CD28 augments IL-2 production by 30- to 100-fold. Using IL-2 RNA accumulation and transcription reporter assays, we have addressed potential mechanisms of CD28 regulation at various time points of stimulation. The kinetic regulation of IL-2 mRNA by TCR and CD28 signals is complex: (i) at the earliest detectable time point, CD28 signalling causes a 20-fold increase compared with TCR signalling alone; (ii) both groups rapidly accumulate mRNA for the first 4 h; (iii) IL-2 mRNA then disappears from cells stimulated through the TCR alone but plateaus or increases slightly in cells costimulated through CD28; and (iv) after 8 h, the mRNA disappears in cultures with the anti-CD28 antibody. Transcription reporter assays did not show a specific effect of CD28 signalling on IL-2 enhancer driven transcription. This was true for either a 353- or a 1.9-kb enhancer, over a broad range of kinetics and TCR occupancy, and with several TCR signal mimics. The early component of CD28 costimulation is nuclear, however, since the initial enhancement of mRNA is also found in unspliced IL-2 RNA. Between 2 and 6 h, there is a marked difference in the rates of decay of IL-2 mRNA in the presence and absence of the CD28 signalling. Rapid decay of IL-2 mRNA commences after 8 h even in the presence of CD28 signals, although the decay occurs at a rate slower than that seen after 4 h of anti-TCR stimulation alone. This complexity suggests the existence of two interesting molecular mechanisms by which CD28 costimulates lymphokine gene expression.
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影响因子：
56.9
作者：
FRASER, JD;IRVING, BA;WEISS, A
通讯作者：
WEISS, A
影响因子：
56.9
作者：
FREEMAN, GJ;GRIBBEN, JG;NADLER, LM
通讯作者：
NADLER, LM
DOI：
10.1073/pnas.90.23.11054
发表时间：
1993-12-01
影响因子：
11.1
作者：
LENSCHOW, DJ;SU, GHT;BLUESTONE, JA
通讯作者：
BLUESTONE, JA
介导小鼠原癌基因 myc 转录减弱的 DNA 序列。
DOI：
10.1073/pnas.86.2.505
发表时间：
1989
影响因子：
11.1
作者：
Wright,S;Bishop,JM
通讯作者：
Bishop,JM
影响因子：
56.9
作者：
EMMEL, EA;VERWEIJ, CL;CRABTREE, GR
通讯作者：
CRABTREE, GR