Transcriptional regulation of the human polymeric immunoglobulin receptor gene by interferon-gamma.

Transcriptional regulation of the human polymeric immunoglobulin receptor gene by interferon-gamma.
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干扰素-γ对人聚合免疫球蛋白受体基因的转录调节。

DOI:
10.1016/s0161-5890(96)00079-x
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发表时间:
1997
影响因子:
3.6
通讯作者:
Kaetzel,CS
Kaetzel,CS
中科院分区:
医学3区
文献类型:
--
作者:
Piskurich,JF;Youngman,KR;Phillips,KM;Hempen,PM;Blanchard,MH;France,JA;Kaetzel,CS

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IgA 通过聚合 Ig 受体 (pIgR) 转运到外部分泌物中。干扰素-γ (IFN-γ) 是 pIgR 表达的主要调节因子,已被证明可以增加 HT-29 人结肠癌细胞中的 pIgR mRNA 水平。为了确定 pIgR 调节的分子机制,分离了含有人 pIgR 基因 5' 侧翼区域的基因组 DNA,并鉴定了人肠上皮细胞中的单个转录起始位点。使用含有 pIgR 基因侧翼区域的嵌合报告质粒,鉴定了 pIgR 启动子的一段片段,该片段对于 HT-29 细胞中 IFN-γ 诱导转录是必要且充分的。值得注意的是,pIgR 启动子包含三个与干扰素刺激反应元件 (ISRE) 同源的基序,其中两个位于 pIgR 基因的 5' 侧翼区域,一个位于外显子 1 中。在用 IFN-γ 刺激后,上游 ISRE 结合 HT-29 细胞组成型表达的核蛋白,而外显子 1 ISRE 结合干扰素调节因子 1 (IRF-1)。此外,IFN-γ对IRF-1启动子的诱导与IFN-γ对pIgR启动子的诱导相关。先前已证明,IFN-γ诱导pIgR mRNA需要从头合成蛋白质。现在表明,在放线菌酮存在下,用 IFN-γ 刺激的 HT-29 细胞的核提取物中未检测到 IRF-1,这表明 IRF-1 的从头合成是 IFN-γ 诱导 pIgR 转录所必需的。
IgA is transported into external secretions by the polymeric Ig receptor (pIgR). Interferon-γ (IFN-γ), a major regulator of pIgR expression, has been shown to increase pIgR mRNA levels in HT-29 human colon carcinoma cells. To determine the molecular mechanisms of pIgR regulation, genomic DNA containing the 5′-flanking region of the human pIgR gene was isolated and a single start site of transcription in human intestinal epithelial cells was identified. Using chimeric reporter plasmids containing flanking regions of the pIgR gene, a segment of the pIgR promoter which is necessary and sufficient for induction of transcription by IFN-γ in HT-29 cells was identified. Significantly, the pIgR promoter contains three motifs homologous to the interferon-stimulated response element (ISRE), two in the 5′-flanking region and one in exon 1 of the pIgR gene. The upstream ISREs bind nuclear protein(s) which are constitutively expressed by HT-29 cells, while the exon 1 ISRE binds interferon regulatory factor-1 (IRF-1), following stimulation with IFN-γ. Furthermore, induction of the IRF-1 promoter by IFN-γ correlates with induction of the pIgR promoter by IFN-γ. It has previously been demonstrated that induction of pIgR mRNA by IFN-γ requires de novo protein synthesis. It is now shown that IRF-1 is not detected in nuclear extracts from HT-29 cells stimulated with IFN-γ in the presence of cycloheximide, suggesting that de novo synthesis of IRF-1 is required for induction of pIgR transcription by IFN-γ.
鉴定影响人类腐烂加速因子基因表达的 5 侧翼区域及其在组织特异性表达中的作用。
DOI: --
发表时间: 1993
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Thomas,DJ;Lublin,DM
通讯作者: Lublin,DM
DOI: 10.1016/0955-0674(94)90144-9
发表时间: 1994-04
影响因子: 7.5
作者:
Ke Shuai
通讯作者: Ke Shuai
DOI: --
发表时间: 1993
期刊: The Journal of biological chemistry
影响因子: --
作者:
Brown,AM;Wright,KL;Ting,JP
通讯作者: Ting,JP
10 – 聚合免疫球蛋白的上皮和肝胆转运
DOI: --
发表时间: 1994
期刊:
影响因子: --
作者:
P. Brandtzaeg;P. Krajči;M. Lamm;C. Kaetzel
通讯作者: C. Kaetzel
α-干扰素诱导含有同源上游序列的 HLA 和金属硫蛋白基因的转录
DOI: --
发表时间: 1985
期刊: Nature
影响因子: 64.8
作者:
R. Friedman;G. Stark
通讯作者: G. Stark