Characterization of Intercellular Adhesion Molecule-1 Regulation by Epstein-Barr Virus-encoded Latent Membrane Protein-1 Identifies Pathways That Cooperate with Nuclear Factor κB to Activate Transcription*
Characterization of Intercellular Adhesion Molecule-1 Regulation by Epstein-Barr Virus-encoded Latent Membrane Protein-1 Identifies Pathways That Cooperate with Nuclear Factor κB to Activate Transcription*
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Epstein-Barr 病毒编码的潜膜蛋白 1 对细胞间粘附分子 1 调节的表征确定了与核因子 κB 协同激活转录的途径*
DOI：
10.1074/jbc.m003758200
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
M. Rowe
中科院分区：
文献类型：
--
作者：
A. Mehl;Eike Floettmann;Matthew Jones;P. Brennan;M. Rowe
Epstein-Barr病毒潜伏膜蛋白-1 （latent membrane protein-1, LMP1）诱导基因转录、表型改变和致癌转化。LMP1诱导的一个细胞基因是细胞间粘附分子-1 (ICAM-1)，它参与了广泛的炎症和免疫反应。ICAM-1可能增强对eb病毒转化细胞的免疫识别，从而对抗恶性肿瘤的发展。尽管对LMP1的各种信号功能的了解越来越多，但LMP1诱导ICAM-1的分子机制尚不清楚。在这里，我们证明LMP1的转录激活完全依赖于ICAM-1启动子的肿瘤坏死因子α (TNFα)应答元件内的一个变异NF-κB基序。尽管TNFα响应元件足以诱导ICAM-1启动子的TNFα，但LMP1还需要其他上游序列的合作才能实现最佳诱导。已知lmp1诱导信号通路的抑制剂研究排除了c-Jun n-末端激酶（JNK）、p38丝裂原活化蛋白激酶和janus活化酪氨酸激酶3 （JAK3）的参与，并证实NF-κB是诱导ICAM-1的关键因子。然而，尽管NF-κB的组成激活有效地诱导启动子活性，但不足以诱导ICAM-1 mRNA或ICAM-1蛋白。利用信号传导缺陷LMP1突变体和去乙酰化抑制剂，我们发现LMP1的c端激活子区1传递了一个新的合作信号来诱导ICAM-1 mRNA。
The latent membrane protein-1 (LMP1) of Epstein-Barr virus induces gene transcription, phenotypic changes, and oncogenic transformation. One cellular gene induced by LMP1 is that for intercellular adhesion molecule-1 (ICAM-1), which participates in a wide range of inflammatory and immune responses. ICAM-1 may enhance the immune recognition of cells transformed by Epstein-Barr virus, and thus combat development of malignancy. Despite growing understanding of the various signaling functions of LMP1, the molecular mechanisms by which LMP1 induces ICAM-1 are not understood. Here, we demonstrate that transcriptional activation by LMP1 is absolutely dependent upon a variant NF-κB motif within the tumor necrosis factor α (TNFα) response element of the ICAM-1 promoter. Although the TNFα response element is sufficient for TNFα induction of the ICAM-1 promoter, LMP1 also required the cooperation of additional upstream sequences for optimal induction. Inhibitor studies of known LMP1-induced signaling pathways ruled out the involvement of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase, and the Janus-activating tyrosine kinase 3 (JAK3), and confirmed NF-κB as a critical factor for induction of ICAM-1. However, although constitutive activation of NF-κB efficiently induced promoter activity, it was not sufficient to induce either ICAM-1 mRNA or ICAM-1 protein. Using signaling defective LMP1 mutants and deacetylation inhibitors, we showed that the C-terminal activator region 1 of LMP1 delivers a new cooperating signal to induce ICAM-1 mRNA.
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影响因子：
4.4
作者：
Michael Loran Dustin;R. Rothlein;A. Bhan;C. Dinarello;T. Springer
通讯作者：
Michael Loran Dustin;R. Rothlein;A. Bhan;C. Dinarello;T. Springer
DOI：
10.1016/s0021-9258(18)35741-7
发表时间：
1992-12
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
C. D. Laherty;Hong-Ming Hu;A. Opipari;F. Wang;V. Dixit
通讯作者：
C. D. Laherty;Hong-Ming Hu;A. Opipari;F. Wang;V. Dixit
DOI：
10.1073/pnas.95.20.11963
发表时间：
1998-09-29
影响因子：
11.1
作者：
Kulwichit, W;Edwards, RH;Raab-Traub, N
通讯作者：
Raab-Traub, N
DOI：
10.1073/pnas.90.19.9150
发表时间：
1993-10-01
影响因子：
11.1
作者：
KAYE, KM;IZUMI, KM;KIEFF, E
通讯作者：
KIEFF, E