Regulation of human LZIP expression by NF-κB and its involvement in monocyte cell migration induced by Lkn-1
Regulation of human LZIP expression by NF-κB and its involvement in monocyte cell migration induced by Lkn-1
复制标题
DOI：
10.1074/jbc.m607962200
复制
发表时间：
2007-04-13
影响因子：
4.8
通讯作者：
Ko, Jesang
中科院分区：
文献类型：
--
作者：
Jang, Sung-Wuk;Kim, Yoon Suk;Ko, Jesang
人LZIP是一种参与白细胞移动性的转录因子。已知LZIP的表达差异调节由CCR 1依赖性趋化因子诱导的单核细胞迁移。然而，其转录调控尚未得到表征。我们的研究结果表明，Lkn-1诱导LZIP表达的时间和剂量依赖性的方式，和LZIP的诱导显示了一个即时的早期响应Lkn-1。我们从人类基因组DNA中鉴定并克隆了类似于1.4kb的LZIP启动子。为了鉴定控制LZIP限制性表达的调控元件，从与荧光素酶报告基因连接的1469-bp LZIP启动子区（-1219/+251）构建缺失突变体。最大的启动子活性包含在613 bp的暂定转录起始位点，并急剧减少在一个截短的构建体（-338/+251）。该启动子序列包含共有的NF-κ B-和Sp-1-结合位点。抑制剂测定的结果显示NF-κ B参与Lkn-1诱导的LZIP表达，但Sp-1不参与。我们还证明了NF-κ B B与LZIP启动子结合，并且这种结合是特异性的，如电泳迁移率变动分析和突变分析所示。趋化性分析表明，由于NF-κ B亚家族的LZIP表达特异性地参与Lkn-1诱导的趋化性。我们的研究结果表明，转录因子NF-κ B在调节LZIP表达中起重要作用，并且LZIP表达调节Lkn-1诱导的单核细胞迁移。
Human LZIP is a transcription factor that is involved in leukocyte cell mobility. Expression of LZIP is known to differentially regulate monocyte cell migration induced by CCR1-dependent chemokines. However, its transcriptional regulation has not been characterized. Our results indicate that Lkn-1 induces LZIP expression in a time- and dose-dependent manner, and the induction of LZIP shows an immediate early response to Lkn-1. We identified and cloned similar to 1.4 kb of the LZIP promoter from a human genomic DNA. To identify regulatory elements controlling restricted expression of LZIP, deletion mutants were constructed from the 1469-bp LZIP promoter region ( - 1219/ + 251) linked to the luciferase reporter gene. Maximal promoter activity was contained within 613 bp from the tentative transcription initiation site and was sharply reduced in a truncated construct ( - 338/ + 251). This promoter sequence contained consensus NF-kappa B- and Sp-1-binding sites. Results from an inhibitor assay showed that NF-kappa B is involved in Lkn-1-induced LZIP expression, but Sp-1 is not. We also demonstrated that NF-kappa B binds to the LZIP promoter and that the binding is specific, as revealed by an electrophoretic mobility shift assay and a mutation analysis. Chemotaxis analysis showed that LZIP expression because of the NF-kappa B subfamily is specifically involved in Lkn-1-induced chemotaxis. Our findings suggest that transcription factor NF-kappa B plays an important role in regulation of LZIP expression, and LZIP expression regulates the monocyte cell migration induced by Lkn-1.