Involvement of Rel, Fos, and Jun proteins in binding activity to the IL-2 promoter CD28 response element/AP-1 sequence in human T cells.
Involvement of Rel, Fos, and Jun proteins in binding activity to the IL-2 promoter CD28 response element/AP-1 sequence in human T cells.
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DOI：
10.4049/jimmunol.159.3.1319
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发表时间：
1997-08
影响因子：
4.4
通讯作者：
Kathleen L. McGuire;M. Iacobelli
中科院分区：
文献类型：
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作者：
Kathleen L. McGuire;M. Iacobelli
CD 28是人T细胞活化过程中重要的共刺激分子。T细胞通过Ag受体和CD 28的共刺激导致高水平的IL-2产生，这对体内免疫应答的发展至关重要。先前的报道已经表明，CD 28刺激通过上调几种转录因子的活性来促进IL-2启动子的激活，所述转录因子包括AP-1和核因子-κ B（NF-kappaB）/Rel家族成员以及称为CD 28应答复合物的未表征的转录因子。虽然一些研究表明NF-κ B/Rel家族成员组成了CD 28应答复合物转录因子，但其他工作并不支持这一结论。最近的研究表明，CD 28反应元件（CD 28 RE）不独立发挥作用，而是与邻近的启动子近端AP-1结合位点一起发挥作用，这一假设在这里得到了证实。此外，在本研究中，评价了与IL-2启动子的CD 28 RE/AP-1序列的结合活性。虽然可以检测到四种特异性复合物与该序列结合，但这些复合物中只有一种对CD 28 RE和相邻的AP-1位点都具有特异性。在所测试的NF-κ B/Rel家族成员中，这种CD 28 RE/AP-1特异性复合物主要含有c-Rel，尽管事实上p50和RelA都可以有效地结合CD 28 RE。c-Fos和c-Jun也存在于这种CD 28 RE/AP-1特异性复合物中。这些数据表明，功能复合物涵盖的CD 28 RE和AP-1结合位点的影响IL-2启动子在CD 28共刺激的T细胞的活性。
CD28 is an important costimulatory molecule in the activation of human T cells. Costimulation of T cells through both the Ag receptor and CD28 leads to high level IL-2 production, which is vital to the development of an immune response in vivo. Previous reports have suggested the CD28 stimulation contributes to the activation of the IL-2 promoter by up-regulating the activity of several transcription factors, including AP-1 and nuclear factor-kappaB (NF-kappaB)/Rel family members as well as an uncharacterized transcription factor called CD28 response complex. While several lines of investigation have suggested that NF-kappaB/Rel family members make up the CD28 response complex transcription factor, other work has not supported this conclusion. Recent studies suggest that the CD28 response element (CD28RE) does not function independently but works instead in conjunction with the adjacent promoter proximal AP-1-binding site and this hypothesis is confirmed here. Also in the current study, binding activity to the CD28RE/AP-1 sequence of the IL-2 promoter is evaluated. Although four specific complexes can be detected binding to this sequence, only one of these complexes is specific for both the CD28RE and the adjacent AP-1 site. Of the NF-kappaB/Rel family members tested, this CD28RE/AP-1-specific complex contains predominantly c-Rel, despite the fact that both p50 and RelA can efficiently bind to the CD28RE. c-Fos and c-Jun are also found in this CD28RE/AP-1-specific complex. These data indicate that functional complexes encompassing both the CD28RE and the AP-1-binding sites influence IL-2 promoter activity in CD28-costimulated T cells.