Cogswell P C, Mayo M W, Baldwin A S
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill 27599-7295, USA.
J Exp Med. 1997 Feb 3;185(3):491-7. doi: 10.1084/jem.185.3.491.
NF-kappa B is an important transcription factor required for T cell proliferation and other immunological functions. The NF-kappa B1 gene encodes a 105-kD protein that is the precursor of the p50 component of NF-kappa B. Previously, we and others have demonstrated that NF-kappa B regulates the NF-kappa B1 gene. In this manuscript we have investigated the molecular mechanisms by which T cell lines stimulated with phorbol 12-myristate 13-acetate (PMA) and phytohemagglutin (PHA) display significantly higher levels of NF-kappa B1 encoding transcripts than cells stimulated with tumor necrosis factor-alpha, despite the fact that both stimuli activate NF-kappa B. Characterization of the NF-kappa B1 promoter identified an Egr-1 site which was found to be essential for both the PMA/PHA-mediated induction as well as the synergistic activation observed after the expression of the RelA subunit of NF-kappa B and Egr-1. Furthermore, Egr-1 induction was required for endogenous NF-kappa B1 gene expression, since PMA/PHA-stimulated T cell lines expressing antisense Egr-1 RNA were inhibited in their ability to upregulate NF-kappa B1 transcription. Our studies indicate that transcriptional synergy mediated by activation of both Egr-1 and NF-kappa B may have important ramifications in T cell development by upregulating NF-kappa B1 gene expression.
核因子-κB是T细胞增殖及其他免疫功能所必需的一种重要转录因子。核因子-κB1基因编码一种105-kD蛋白，该蛋白是核因子-κB的p50组分的前体。此前，我们及其他研究人员已证实核因子-κB可调节核因子-κB1基因。在本论文中，我们研究了如下分子机制：用佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）和植物血凝素（PHA）刺激的T细胞系，与用肿瘤坏死因子-α刺激的细胞相比，显示出显著更高水平的核因子-κB1编码转录本，尽管这两种刺激均可激活核因子-κB。对核因子-κB1启动子的特性分析确定了一个早期生长反应因子-1（Egr-1）位点，发现该位点对于PMA/PHA介导的诱导以及在核因子-κB的RelA亚基和Egr-1表达后观察到的协同激活均至关重要。此外，Egr-1的诱导是内源性核因子-κB1基因表达所必需的，因为表达反义Egr-1 RNA的PMA/PHA刺激的T细胞系上调核因子-κB1转录的能力受到抑制。我们的研究表明，由Egr-1和核因子-κB的激活介导的转录协同作用可能通过上调核因子-κB1基因表达在T细胞发育中具有重要影响。
