Regulation of major vault protein expression by upstream stimulating factor 1 in SW620 human colon cancer cells
Regulation of major vault protein expression by upstream stimulating factor 1 in SW620 human colon cancer cells
复制标题
DOI：
10.3892/or.2013.2818
复制
发表时间：
2014-01-01
期刊：
影响因子：
4.2
通讯作者：
Takeda, Yasuo
中科院分区：
文献类型：
--
作者：
Ikeda, Ryuji;Nishizawa, Yukihiko;Takeda, Yasuo
主要穹窿蛋白 (MVP) 是穹窿核糖核蛋白颗粒的主要成分，与肺阻力相关蛋白 (LRP) 相同。尽管 MVP 也在多种类型的正常组织中表达，但对其生理作用知之甚少。在本研究中，我们确定了调节 MVP 表达的关键 MVP 启动子元件。对组织表达谱的检查显示，MVP 在心脏、胎盘、肺、肝脏、肾脏和胰腺中表达。 MVP 启动子的元件包含转录因子、STAT、p53、Sp1、E-box、GATA、MyoD 和 Y-box 的结合位点。通过缺失分析，保守的近端 E-box 结合位点被证明对于人类 MVP 启动子反式激活非常重要。引入针对上游刺激因子 (USF) 1 的 siRNA（已知该因子与 E-box 结合位点结合）可降低 SW620 和 ACHN 细胞中 MVP 的表达。使用染色质免疫沉淀 (ChIP) 测定，USF1 结合 SW620 细胞中的 MVP 启动子。这些发现表明 USF1 与 E-box 元件的结合可能对于基础 MVP 启动子激活至关重要。本研究结果有助于理解调节 MVP 基因表达的分子机制，并可能有助于阐明 MVP 的生理功能。
Major vault protein (MVP) is the main constituent of the vault ribonucleoprotein particle and is identical to lung resistance-related protein (LRP). Although MVP is also expressed in several types of normal tissues, little is known about its physiological role. In the present study, we identified the crucial MVP promoter elements that regulate MVP expression. An examination of tissue expression profiles revealed that MVP was expressed in the heart, placenta, lung, liver, kidney and pancreas. Elements of the MVP promoter contain binding sites for transcription factors, STAT, p53, Sp1, E-box, GATA, MyoD and Y-box. By deletion analysis, a conserved proximal E-box binding site was demonstrated to be important for human MVP promoter transactivation. Introduction of siRNA against upstream stimulating factor (USF) 1, which is known to bind the E-box binding site, decreased the expression of MVP in SW620 and ACHN cells. Using a chromatin immunoprecipitation (ChIP) assay, USF1 bound the MVP promoter in SW620 cells. These findings suggest that USF1 binding to an E-box element may be critical for basal MVP promoter activation. The results of the present study are useful in understanding the molecular mechanisms regulating MVP gene expression, and may aid in elucidating the physiological functions of MVP.