A retrovirus restriction factor TRIM5α is transcriptionally regulated by interferons
A retrovirus restriction factor TRIM5α is transcriptionally regulated by interferons
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DOI：
10.1016/j.bbrc.2005.10.173
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发表时间：
2005-12-30
影响因子：
3.1
通讯作者：
Inoue, S
中科院分区：
文献类型：
--
作者：
Asaoka, K;Ikeda, K;Inoue, S
TRIM5 α是三方基序蛋白家族的成员，最近被确定为一种物种特异性的逆转录病毒感染的限制因子。人类TRIN15 α基因与TRIM6、21、22、34等TRIM基因位于染色体11p15位点。通过Northern blot分析和实时荧光定量PCR，我们发现干扰素（IFN）上调HeLa和HepG2细胞中TRIM5 α mRNA的表达。TRIM5 α启动子活性是IFN诱导的，荧光素酶测定证实了这一点，使用含有TRIM5 α 5 '-侧翼区域的报告质粒。突变分析表明，ifn通过假定的干扰素刺激反应元件（ISRE）激活TRIM5 α启动子活性。有趣的是，另一种ifn响应蛋白信号传感器和转录因子I激活因子（STAT1）结合到ISRE序列上，这是用HeLa细胞提取物进行的电泳迁移转移试验所显示的。我们提出了一种针对TRIM5ot的特异性多克隆抗体，并证实了TRIM5ot蛋白在HeLa细胞中可被ifn - β诱导表达。这些结果使我们确定TRIM5 α的转录和蛋白质合成可以被IFN调节，这表明TRIM5 α可能在IFN诱导的抗逆转录病毒感染的抗病毒状态中发挥作用。(c) 2005爱思唯尔公司版权所有。
TRIM5 alpha is a member of tripartite motif protein family and recently identified as a restriction factor for retroviral infection in a species-specific manner. Human TRIN15 alpha gene is located on chromosomal position 11p15 in a cluster with other TRIM genes including TRIM6, 21, 22, and 34. We show here that interferon (IFN) upregulates TRIM5 alpha mRNA expression in HeLa and HepG2 cells by performing Northern blot analysis and quantitative real-time PCR. TRIM5 alpha promoter activity was IFN inducible as confirmed by luciferase assay using a reporter plasmid that contained the 5 '-flanking region of TRIM5 alpha. Mutational analysis has revealed that IFNs activate TRIM5 alpha promoter activity through a putative in terferon- stimulated response element (ISRE). Intriguingly, another IFN-responsive protein signal transducer and activator of transcription factor I (STAT1) binds to the ISRE sequence as shown by electrophoretic mobility shift assay using HeLa cell extracts. We have raised a specific polyclonal antibody against TRIM5ot and confirmed that TRIM5ot protein expression is inducible by IFN-beta in HeLa cells. These results lead us to define that the transcription and protein synthesis of TRIM5 alpha could be modulated by IFN, suggesting that TRIM5 alpha may play a role in an IFN-induced antiviral state against retrovirus infection. (c) 2005 Elsevier Inc. All rights reserved.