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紫外线照射后,RhoB信使核糖核酸(mRNA)由HuR蛋白稳定下来。

RhoB mRNA is stabilized by HuR after UV light.

作者信息

Westmark Cara J, Bartleson Virginia B, Malter James S

机构信息

Department of Pathology and Laboratory Medicine, Waisman Center for Developmental Disabilities, University of Wisconsin, Madison, WI 53705, USA.

出版信息

Oncogene. 2005 Jan 13;24(3):502-11. doi: 10.1038/sj.onc.1208224.

Abstract

RhoB is a small GTP-binding protein that is involved in apoptotic signal transduction. We have cloned the mouse RhoB mRNA including a 1377 nucleotide 3'-untranslated region (UTR) that contains six AU-rich elements (AREs) as well as several uridine-rich stretches. There is 94% homology overall between the mouse and rat RhoB genes and 92% homology between the mouse and a putative human clone. Ultraviolet light (UVL) induces RhoB production through regulated changes in gene transcription and mRNA stabilization although the latter mechanism is unknown. We observed that UVL increased the half-life of RhoB mRNA from 63 min to 3.3 h in NIH/3T3 cells and from 87 min to 2.7 h in normal human keratinocyte cells. In vitro mobility shift assays demonstrated that HuR bound the 3'-UTR of RhoB at three distinct locations (nucleotides 1342-1696, 1765-1920 and 1897-1977) suggesting a regulatory role for this RNA-binding protein. HuR immunoprecipitations were positive for RhoB mRNA indicating an in vivo association, and Western blot analysis and immunofluorescence demonstrated that HuR rapidly partitions from the nucleus to the cytoplasm after UVL. Therefore, we propose a model in which UVL induces stress-activated signal transduction leading to nuclear/cytoplasmic shuttling of HuR and subsequent stabilization of RhoB mRNA.

摘要

RhoB是一种参与凋亡信号转导的小GTP结合蛋白。我们克隆了小鼠RhoB mRNA,其包含一个1377个核苷酸的3'非翻译区(UTR),该区域含有六个富含AU的元件(ARE)以及几个富含尿苷的片段。小鼠和大鼠的RhoB基因之间总体上有94%的同源性,小鼠和一个推定的人类克隆之间有92%的同源性。紫外线(UVL)通过基因转录和mRNA稳定性的调节变化诱导RhoB产生,尽管后一种机制尚不清楚。我们观察到,UVL使NIH/3T3细胞中RhoB mRNA的半衰期从63分钟增加到3.3小时,在正常人角质形成细胞中从87分钟增加到2.7小时。体外迁移率变动分析表明,HuR在三个不同位置(核苷酸1342 - 1696、1765 - 1920和1897 - 1977)与RhoB的3'-UTR结合,表明这种RNA结合蛋白具有调节作用。HuR免疫沉淀对RhoB mRNA呈阳性,表明存在体内关联,蛋白质印迹分析和免疫荧光表明,UVL照射后HuR迅速从细胞核转移到细胞质。因此,我们提出了一个模型,其中UVL诱导应激激活的信号转导,导致HuR在细胞核/细胞质之间穿梭,并随后稳定RhoB mRNA。

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