Tax is Involved in Up-regulation of HMGB1 Expression Levels by Interaction with C/EBP
Tax is Involved in Up-regulation of HMGB1 Expression Levels by Interaction with C/EBP
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税收通过与 C/EBP 相互作用上调 HMGB1 表达水平
DOI：
10.7314/apjcp.2013.14.1.359
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发表时间：
2013-01-01
影响因子：
--
通讯作者：
Hu, Li-Hua
中科院分区：
文献类型：
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作者：
Zhang, Chen-Guang;Wang, Hui;Hu, Li-Hua
高迁移率族蛋白1（HMGB1）蛋白是一种多功能细胞因子样分子，在肿瘤的发病机制中发挥着重要作用。在这项研究中，实时聚合酶链反应和蛋白质印迹分析表明，Tax(+)-T 细胞 (TaxP) 中 HMGB1 转录活性和蛋白水平增加。为了阐明其机制，将一系列 HMGB1 缺失报告质粒（pHLuc1 至 pHLuc6）转染到 Tax(-)-T 细胞（TaxN、Jurkat）和 Tax(+)-T 细胞（TaxP）中。我们发现Tax(+)-T细胞中的启动子活性高于Tax(-)-T细胞中的启动子活性，表明pHLuc6显着增加。 Bay11-7082（NF-aleph B抑制剂）治疗并没有阻止增强作用。染色质免疫沉淀分析显示，Tax 保留在包含 -1163 至 -975 的 HMGB1 启动子片段上。生物信息学分析显示，相关片段中有 CdxA、AP-1、AML-1a、USF、v-Myb 和 C/EBP 的六个特征顺式元件。 C/EBP 顺式元件突变显着降低了 Tax 诱导的 HMGB1 启动子活性。这些发现表明，Tax 可能通过与 C/EBP 相互作用，在转录水平上增强 HMGB1 基因的表达。
The high mobility group box 1 (HMGB1) protein is a multifunctional cytokine-like molecule that plays an important role in the pathogenesis of tumors. In this study, real-time polymerase chain reactions and Western blot assays indicated that HMGB1 transcriptional activity and protein level are increased in Tax(+)-T cells (TaxP). To clarify the mechanisms, a series of HMGB1 deletion reporter plasmids (pHLuc1 to pHLuc6) were transfected into Tax(-)-T cells (TaxN, Jurkat) and Tax(+)-T cells (TaxP). We found that promoter activity in Tax(+)-T cells to be higher than that in Tax(-)-T cells, indicating a significant increase in pHLuc6. Bay11-7082 (NF-aleph B inhibitor) treatment did not block the enhancing effect. Chromatin immunoprecipitation assays revealed that Tax was retained on a HMGB1 promoter fragment encompassing -1163 to -975. Bioinformatics analysis showed six characteristic cis-elements for CdxA, AP-1, AML-1a, USF, v-Myb, and C/EBP in the fragment in question. Mutation of cis-elements for C/EBP reduced significant HMGB1 promoter activity induced by Tax. These findings indicate that Tax enhances the expression of HMGB1 gene at the transcriptional level, possibly by interacting with C/EBP.