Discrimination between RelA and RelB transcriptional regulation by a dominant negative mutant of IκBα
Discrimination between RelA and RelB transcriptional regulation by a dominant negative mutant of IκBα
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DOI：
10.1074/jbc.273.1.592
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发表时间：
1998-01-02
影响因子：
4.8
通讯作者：
Körner, M
中科院分区：
文献类型：
--
作者：
Ferreira, V;Tarantino, N;Körner, M
RelA 和 RelB 属于核因子 kappa B (NF-kappa B-Rel) 转录因子家族。两种蛋白质在结构和功能上相关，但它们的细胞内和组织分布不同。在静息细胞中，RelB主要存在于细胞核中，而RelA则被蛋白质抑制剂隔离在细胞质中，其中I kappa B α是淋巴细胞中的主要形式。细胞激活后，I kappa B α 被蛋白水解，使 RelA 二聚体进入细胞核并激活靶基因。为了研究 RelA 和 RelB 基因调控的选择性，我们生成了稳定表达 I kappa B α 显性失活突变体的 T 细胞系。我们发现，选择性抑制 RelA-NF-kappa B 会降低 NPKB1、白细胞介素 2 和白细胞介素 2R α 基因的诱导，但不会降低 c-myc。由 I kappa B α 启动子驱动的转录被转基因 I kappa B α 阻断；然而，野生型 I kappa B α 在转基因细胞克隆中表达，但动力学比对照细胞慢得多。野生型 I kappa B α 表达伴随着 RelB 上调，表明 RelB 可能通过与替代位点结合参与 I kappa B α 的转录。这些结果表明 RelB 和 RelA 对基因表达具有不同且重叠的影响。
RelA and RelB belong to the nuclear factor-kappa B (NF-kappa B-Rel) transcription factor family. Both proteins are structurally and functionally related, but their intracellular and tissue distributions are different. In resting cells, RelB is found mostly in the nucleus, whereas RelA is sequestered in the cytosol by protein inhibitors, among which I kappa B alpha is the dominant form in lymphocytes. Upon cellular activation I kappa B alpha is proteolyzed, allowing RelA dimers to enter the nucleus and activate target genes. To study the selectivity of gene regulation by RelA and RelB, we generated T cell lines stably expressing a dominant negative mutant of I kappa B alpha. We show that selective inhibition of RelA-NF-kappa B decreased induction of NPKB1, interleukin-2, and interleukin-2R alpha genes but not c-myc. Transcription driven by the I kappa B alpha promoter was blocked by the transgenic I kappa B alpha; however, wild type I kappa B alpha was expressed in the transgenic cell clones but with much slower kinetics than that in control cells. Wild type I kappa B alpha expression was concomitant with RelB up-regulation, suggesting that RelB could be involved in transcription of I kappa B alpha through binding to an alternative site. These results indicate that RelB and RelA have both distinct and overlapping effects on gene expression.