Epstein-Barr virus encoded latent membrane protein 1 modulates nuclear translocation of telomerase reverse transcriptase protein by activating nuclear factor-κB p65 in human nasopharyngeal carcinoma cells
Epstein-Barr virus encoded latent membrane protein 1 modulates nuclear translocation of telomerase reverse transcriptase protein by activating nuclear factor-κB p65 in human nasopharyngeal carcinoma cells
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DOI：
10.1016/j.biocel.2005.04.012
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发表时间：
2005-09-01
影响因子：
4
通讯作者：
Cao, Y
中科院分区：
文献类型：
--
作者：
Ding, L;Li, LL;Cao, Y
癌细胞的持续增殖需要端粒酶维持染色体稳定性并延长端粒长度调节的细胞复制。人端粒酶逆转录酶（Human telomerase reverse transcriptase，hTERT）是人端粒酶催化亚单位，也是人端粒酶活性的关键决定因子，在转录水平上受到调控，并通过磷酸化和转位进行调控。在本研究中，我们发现潜伏膜蛋白1（LMP 1），EB病毒（EBV）的主要癌蛋白，调节端粒酶活性的诱导hTERT直接结合到核因子κ B（NF-κ B B）p65和两个蛋白质从细胞质易位到细胞核中的鼻咽癌细胞（NPC）。相反，NF-κ B核转位抑制剂（苄基羰基）-Leu-Leu-苯丙氨酸（Z-LLF-CHO）和NF-κ B抑制剂的显性负突变体（I κ B α）可以阻断LMP 1诱导的hTERT核转位。这些研究提示LMP 1具有一种新的功能，并证实NF-κ B B在调节鼻咽癌细胞端粒酶活化和核转位中起重要作用。(C)2005爱思唯尔有限公司保留所有权利。
Sustained proliferation of cancer cells requires that telomerase maintain chromosomal stability and prolong telomere length-regulated cell replication. Human telomerase reverse transcriptase (hTERT), the human telomerase catalytic subunit, and also the key determinant of the enzymatic activity of human telomerase, is regulated both at the transcriptional level and via phosphorylation and translocation. In this study, we show that latent membrane protein 1(LMP1), the principal oncoprotein of Epstein-Barr virus (EBV), modulates telomerase activity by inducing the direct binding of hTERT to nuclear factor kappa B (NF-kappa B) p65 and translocation of both proteins from the cytoplasm to the nucleus in nasopharyngeal carcinoma cells (NPC). Conversely, a NF-kappa B nuclear translocation inhibitor, (benzylcarbonyl)-Leu-Leu-phenylalaninal (Z-LLF-CHO), and a dominant negative mutant of inhibitor of NF kappa B (I kappa B alpha), can block LMP1-induced hTERT nuclear translocation. These studies suggest a novel function of LMP1 and confirm that NF-kappa B plays an important role in regulating the activation and nuclear translocation of telomerase in NPC cells. (C) 2005 Elsevier Ltd. All rights reserved.