Shapiro V S, Mollenauer M N, Greene W C, Weiss A
Department of Medicine, University of California San Francisco, California 94143, USA.
J Exp Med. 1996 Nov 1;184(5):1663-9. doi: 10.1084/jem.184.5.1663.
T cell activation by antigen/MHC induces the expression of several genes critical to the immune response, including interleukin-2. T cells from mice deficient for the NF-kappa B family member c-rel cannot activate IL-2 gene expression. However, mutating the NF-kappa B site in the IL-2 promoter has only moderate effects. To investigate additional ways c-Rel could regulate IL-2 gene expression, we determined whether c-rel overexpression could increase the activity of other transcription factors involved in IL-2 promoter regulation: NF-AT, Oct/OAP (ARRE-1), and AP-1. In Jurkat TAg cells, overexpression of c-Rel increased AP-1 activation approximately 17-fold. Moreover, AP-1 activity stimulated by anti-TCR Abs or PMA/ionomycin was further increased by c-Rel overexpression. c-Rel overexpression did not affect NF-AT or ARRE-1 activity. Additionally, overexpression of c-Rel activated the nonconsensus AP-1 site from the IL-2 promoter (NF-IL-2B), although to a lesser extent, approximately sixfold. AP-1 activation required both the DNA binding and transactivation domains of c-Rel. Our results may provide an explanation for the effect on IL-2 gene activation in c-rel-deficient mice.
抗原/MHC介导的T细胞活化可诱导多种对免疫反应至关重要的基因表达，包括白细胞介素-2。来自NF-κB家族成员c-rel基因缺陷小鼠的T细胞无法激活白细胞介素-2基因的表达。然而，在白细胞介素-2启动子中突变NF-κB位点仅有中等程度的影响。为了研究c-Rel调节白细胞介素-2基因表达的其他方式，我们确定了c-rel过表达是否能增加参与白细胞介素-2启动子调节的其他转录因子的活性：活化T细胞核因子（NF-AT）、八聚体结合蛋白/Octamer结合蛋白（Oct/OAP，抗原受体反应元件-1，ARRE-1）和活化蛋白-1（AP-1）。在Jurkat TAg细胞中，c-Rel的过表达使AP-1的活化增加了约17倍。此外，抗T细胞受体抗体或佛波酯/离子霉素刺激的AP-1活性因c-Rel过表达而进一步增加。c-Rel过表达不影响NF-AT或ARRE-1的活性。此外，c-Rel的过表达激活了白细胞介素-2启动子的非共有AP-1位点（NF-IL-2B），尽管程度较小，约为6倍。AP-1的活化需要c-Rel的DNA结合结构域和反式激活结构域。我们的结果可能为c-rel基因缺陷小鼠中白细胞介素-2基因激活的影响提供一个解释。
