Epstein-Barr virus latent membrane protein 1 trans-activates miR-155 transcription through the NF-kappaB pathway.
Epstein-Barr virus latent membrane protein 1 trans-activates miR-155 transcription through the NF-kappaB pathway.
复制标题
DOI：
10.1093/nar/gkn666
复制
发表时间：
2008-11
影响因子：
14.9
通讯作者：
Mallardo M
中科院分区：
文献类型：
--
作者：
Gatto G;Rossi A;Rossi D;Kroening S;Bonatti S;Mallardo M
EB病毒（EBV）编码的潜伏膜蛋白-1（LMP 1）是肿瘤坏死因子受体家族的功能同源物，其通过激活核因子-κB（NF-κB）而显著促进EBV的致癌潜力。miR-155是一种致癌的miRNA，对B细胞成熟和免疫球蛋白响应抗原的产生至关重要。我们报道了miR-155在EBV永生化B细胞中的表达比在EBV阴性B细胞中高得多。当转染EBV阴性B细胞时，LMP 1而非LMP 2上调miR-155的表达。我们分析了miR-155启动子中两个推定的NF-κB结合位点;在EBV永生化细胞的核提取物中，这两个位点都募集了NF-κB复合物。在EBV阴性背景下，LMP 1的外源性表达与NF-κB位点结合的p65诱导和miR-155过表达在时间上相关。p65结合的诱导与RNA聚合酶II结合的增加一起证实了LMP 1介导的miR-155的激活在转录上发生。在报告基因分析中，缺乏NF-κB结合位点的miR-155启动子不再被LMP 1表达激活，需要完整的AP 1位点才能获得最大激活。最后，我们证明了在EBV阴性背景下LMP 1介导的miR-155活化与蛋白PU.1的减少相关，PU.1是一个可能的miR靶点。
The Epstein–Barr virus (EBV)-encoded latent membrane protein-1 (LMP1), a functional homologue of the tumor necrosis factor receptor family, substantially contributes to EBV's oncogenic potential by activating nuclear factor-κB (NF-κB). miR-155 is an oncogenic miRNA critical for B-cell maturation and immunoglobulin production in response to antigen. We report that miR-155 expression is much higher in EBV-immortalized B cells than in EBV-negative B cells. LMP1, but not LMP2, up-regulated the expression of miR-155, when transfected in EBV-negative B cells. We analyzed two putative NF-κB binding sites in the miR-155 promoter; both sites recruited NF-κB complex, in nuclear extract from EBV-immortalized cells. The exogenous expression of LMP1, in EBV-negative background, is temporally correlated to induction of p65 with binding on both NF-κB sites and with miR-155 overexpression. The induction of p65 binding together with increased RNA polymerase II binding, confirms that LMP1-mediated activation of miR-155 occurs transcriptionally. In reporter assays, miR-155 promoter lacking NF-κB binding sites was no longer activated by LMP1 expression and an intact AP1 site is needed to attain maximum activation. Finally, we demonstrate that LMP1-mediated activation of miR-155 in an EBV-negative background correlates with reduction of protein PU.1, which is a possible miR target.
登录
查看更多内容
DOI：
10.1126/science.1139253
发表时间：
2007-04-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Rodriguez A;Vigorito E;Clare S;Warren MV;Couttet P;Soond DR;van Dongen S;Grocock RJ;Das PP;Miska EA;Vetrie D;Okkenhaug K;Enright AJ;Dougan G;Turner M;Bradley A
通讯作者：
Bradley A
影响因子：
5.4
作者：
Cameron, Jennifer E.;Yin, Qinyan;Flemington, Erik K.
通讯作者：
Flemington, Erik K.
DOI：
10.1073/pnas.0602266103
发表时间：
2006-05-02
影响因子：
11.1
作者：
Costinean, S;Zanesi, N;Croce, CM
通讯作者：
Croce, CM
影响因子：
8
作者：
Eliopoulos, AG;Caamano, JH;Young, LS
通讯作者：
Young, LS
影响因子：
56.9
作者：
BROWN, K;GERSTBERGER, S;SIEBENLIST, U
通讯作者：
SIEBENLIST, U