Metastases suppressor NME2 associates with telomere ends and telomerase and reduces telomerase activity within cells.
Metastases suppressor NME2 associates with telomere ends and telomerase and reduces telomerase activity within cells.
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DOI：
10.1093/nar/gkr1109
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发表时间：
2012-03
影响因子：
14.9
通讯作者：
Chowdhury S
中科院分区：
文献类型：
--
作者：
Kar A;Saha D;Purohit G;Singh A;Kumar P;Yadav VK;Kumar P;Thakur RK;Chowdhury S
染色质免疫沉淀分析后测序（ChIP-seq）通常会忽略未在结合位置（峰）内映射的序列读数。使用无偏方法，我们分析了所有读数，包括映射的读数和未作为峰的一部分包括的读数。在人肺腺癌和纤维肉瘤细胞中进行ChIP-seq实验，用于转移抑制因子非转移性2（NME 2）。令人惊讶的是，我们确定了在两种情况下唯一代表人类端粒末端的序列读数。使用独立的方法验证了端粒末端NME 2的体内存在，并且作为进一步的证据，我们发现了NME 2和端粒重复序列结合因子2的核内关联。最值得注意的是，结果表明，NME 2与端粒酶相关并在体外和体内降低端粒酶活性，并且持续的NME 2表达导致侵袭性人类癌细胞中端粒长度减少。NME 2的抗转移功能已在人类癌症中得到证实，然而，机制知之甚少。总之，本文报道的研究结果表明NME 2作为端粒结合蛋白的新作用，可以改变端粒酶功能和端粒长度。这提供了一个机会，研究端粒相关的相互作用，在转移抑制。
Analysis of chromatin-immunoprecipitation followed by sequencing (ChIP-seq) usually disregards sequence reads that do not map within binding positions (peaks). Using an unbiased approach, we analysed all reads, both that mapped and ones that were not included as part of peaks. ChIP-seq experiments were performed in human lung adenocarcinoma and fibrosarcoma cells for the metastasis suppressor non-metastatic 2 (NME2). Surprisingly, we identified sequence reads that uniquely represented human telomere ends in both cases. In vivo presence of NME2 at telomere ends was validated using independent methods and as further evidence we found intranuclear association of NME2 and the telomere repeat binding factor 2. Most remarkably, results demonstrate that NME2 associates with telomerase and reduces telomerase activity in vitro and in vivo, and sustained NME2 expression resulted in reduced telomere length in aggressive human cancer cells. Anti-metastatic function of NME2 has been demonstrated in human cancers, however, mechanisms are poorly understood. Together, findings reported here suggest a novel role for NME2 as a telomere binding protein that can alter telomerase function and telomere length. This presents an opportunity to investigate telomere-related interactions in metastasis suppression.
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DOI：
10.1186/bcr553
发表时间：
2003
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Artandi SE
通讯作者：
Artandi SE
影响因子：
46.9
作者：
Ji, Hongkai;Jiang, Hui;Ma, Wenxiu;Johnson, David S.;Myers, Richard M.;Wong, Wing H.
通讯作者：
Wong, Wing H.
影响因子：
56.9
作者：
Azzalin, Claus M.;Reichenbach, Patrick;Lingner, Joachim
通讯作者：
Lingner, Joachim
影响因子：
3
作者：
Fournier, HN;Albigès-Rizo, C;Block, MR
通讯作者：
Block, MR
影响因子：
14.9
作者：
Cawthon, RM
通讯作者：
Cawthon, RM