Coordinated regulation of the promoter and enhancer regions of human CD23 gene by signal through IL-4R and CD40, and the role of Ku70/80 in the enhancer activity.
Coordinated regulation of the promoter and enhancer regions of human CD23 gene by signal through IL-4R and CD40, and the role of Ku70/80 in the enhancer activity.
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DOI：
10.11480/jmds.500203
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发表时间：
2003-06
影响因子：
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通讯作者：
M. Imai;S. Mizutani;T. Morio
中科院分区：
文献类型：
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作者：
M. Imai;S. Mizutani;T. Morio
CD23在细胞增殖、抗原摄取和提呈以及免疫球蛋白E的生成中起作用。通过IL-4R和CD40的信号刺激B细胞中CD23的转录，这是免疫球蛋白类转换(IGCs)所必需的。同样的信号诱导人类静息B细胞中Ku的核转位，这也是IGCs所必需的，这表明这些信号通路是相连的。我们检测了CD23基因的调控，并将最小启动子定位在-132+80区域。一对188个碱基的反向重复序列抑制了其活性。内含子区域包括EBV反应元件(EBVRE)及其周围序列，需要基因特异性启动子来增强报告基因的活性。用重组EBV感染的DND39B细胞的亚克隆进行Western blotting和FACS分析，发现CD23上调与EBNA 2和LMP 1的表达没有必然的相关性。虽然Ku与EBVRE没有特异性结合，但显性阴性的Ku80抑制了IL-4+抗CD40诱导的CD23的表达。这些结果表明Ku作为信号转导和基因增强参与了基因调控。对CD23基因调控的详细分析将有助于更好地理解过敏和淋巴增殖等疾病。
CD23 has roles in proliferation, antigen uptake and presentation, and the generation of IgE. Signals through IL-4R and CD40 stimulate transcription of CD23 in B cells and are necessary for immunoglobulin class switch (IgCS). The same signals induce nuclear translocation of Ku, which is also required for IgCS, in human resting B cells, suggesting that these signaling pathways are connected. We examined the regulation of CD23 gene, and located the minimal promoter at -132+80 region. A pair of 188bp inverted repeats inhibited its activity. The intronic region including EBV responsive element (EBVRE) and the surrounding sequence, required the gene specific promoter to enhance the reporter gene activity. Western blotting and FACS analysis using subclones of DND39 B cells infected with recombinant EBV, revealed that CD23 upregulation did not necessarily correlate with EBNA 2 and LMP 1 expression. Although the specific binding of Ku to EBVRE was not demonstrated, dominant negative Ku80 suppressed IL-4 + anti-CD40-driven CD23 expression. These results suggest that Ku is involved in gene regulation as a signal transducer and gene enhance. Detailed analysis of CD23 gene regulation would lead to a better understanding of disorders such as allergy and lymphoproliferation.