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首页> 外文期刊>Molecular and Cellular Biology >RelA is a potent transcriptional activator of the CD28 response element within the interleukin 2 promoter.
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RelA is a potent transcriptional activator of the CD28 response element within the interleukin 2 promoter.

机译：RelA是白介素2启动子内CD28反应元件的有效转录激活因子。

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T-cell activation requires two different signals. The T-cell receptor's recognition of a specific antigen on antigen-presenting cells provides one, and the second signal comes from costimulatory molecules such as CD28. In contrast, T cells that are stimulated with antigen in the absence of the CD28 costimulatory signal can become anergic (nonresponsive). The CD28 response element (CD28RE) has been identified as the DNA element mediating interleukin 2 (IL-2) gene activation by CD28 costimulation. Our previous work demonstrates that the Rel/NF-kappa B family proteins c-Rel, RelA (p65), and NFKB1 (p50) are involved in the complex that binds to the CD28RE. We also showed that c-Rel, but not NFKB1 (p50), can bind to the CD28RE and activate CD28RE-driven transcription in cotransfection assays. However, the role of RelA (p65) in CD28 signaling has not yet been addressed. We provide evidence that RelA (p65) itself bound directly to the CD28RE of the IL-2 promoter and other lymphokine promoters. In addition, RelA (p65) was a potent transcriptional activator of the CD28RE in vivo. We show that a RelA (p65)-c-Rel heterodimer bound to the CD28RE and synergistically activated the CD28RE enhancer activity. We also demonstrate that activated Raf-1 kinase synergized with RelA (p65) in activating the CD28RE enhancer activity. Interestingly, a soluble anti-CD28 monoclonal antibody alone, in the absence of other stimuli, also synergized with RelA (p65) in activating the CD28RE. Furthermore, we show that RelA (p65) activated expression of the wild-type IL-2 promoter but not the CD28RE-mutated IL-2 promoter. A combination of RelA (p65) and NFKB1 (p50) also activated the IL-2 promoter through the CD28RE site. These results demonstrate the functional regulation of the CD28RE, within the IL-2 promoter, by Rel/NF-kappa B transcription factors.
机译：T细胞激活需要两个不同的信号。 T细胞受体对抗原呈递细胞上特定抗原的识别提供了一种，第二种信号来自共刺激分子，例如CD28。相反，在没有CD28共刺激信号的情况下被抗原刺激的T细胞可能变得无反应（无反应）。 CD28反应元件（CD28RE）已被鉴定为通过CD28共刺激介导白介素2（IL-2）基因激活的DNA元件。我们以前的工作表明，Rel /NF-κB家族蛋白c-Rel，RelA（p65）和NFKB1（p50）参与了与CD28RE结合的复合物。我们还显示了c-Rel，但不是NFKB1（p50），可以与CD28RE结合并在共转染测定中激活CD28RE驱动的转录。但是，RelA（p65）在CD28信号中的作用尚未得到解决。我们提供证据，RelA（p65）本身直接绑定到IL-2启动子和其他淋巴因子启动子的CD28RE。此外，RelA（p65）是体内CD28RE的有效转录激活因子。我们显示，RelA（p65）-c-Rel异二聚体与CD28RE结合并协同激活CD28RE增强子活性。我们还证明了激活的Raf-1激酶与RelA（p65）在激活CD28RE增强剂活性中具有协同作用。有趣的是，在没有其他刺激的情况下，单独的可溶性抗CD28单克隆抗体在激活CD28RE时也与RelA（p65）协同作用。此外，我们显示RelA（p65）激活野生型IL-2启动子的表达，但不激活CD28RE突变的IL-2启动子。 RelA（p65）和NFKB1（p50）的组合也通过CD28RE位点激活了IL-2启动子。这些结果证明了Rel /NF-κB转录因子在IL-2启动子内对CD28RE的功能调节。

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