Human cytomegalovirus immediate-early protein promotes survival of glioma cells through interacting and acetylating ATF5.
Human cytomegalovirus immediate-early protein promotes survival of glioma cells through interacting and acetylating ATF5.
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人巨细胞病毒立即早期蛋白通过相互作用和乙酰化 ATF5 促进神经胶质瘤细胞的存活
DOI：
10.18632/oncotarget.17150
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发表时间：
2017-05-09
期刊：
影响因子：
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通讯作者：
Liu DX
中科院分区：
文献类型：
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作者：
Hu M;Wang B;Qian D;Wang M;Huang R;Wei L;Li L;Zhang L;Liu DX
人类巨细胞病毒 (HCMV) 是一种广泛传播的 β-疱疹病毒，可感染高比例的神经胶质瘤。 HCMV 在人类神经胶质瘤中以低水平表达被特异性检测到，这提出了它可能以慢性方式调节恶性表型的可能性。尽管 HCMV 不被认为是致癌病毒，但它可能会失调参与恶性肿瘤发生和促进的信号通路。在这里，我们的免疫组织化学染色显示，与非肿瘤样本 (4.20%) 和低级别胶质瘤 (19.56%) 相比，GBM (58.56%) 中 HCMV 86-kDa 即早期蛋白 (IE86) 的核染色显着增加。 IE86 染色与激活转录因子 5 (ATF5) 的染色呈正相关，这对于神经胶质瘤细胞的活力和增殖至关重要，表明 HCMV IE86 可能在神经胶质瘤生物学中具有重要意义。此外，我们发现IE86过表达可增强神经胶质瘤细胞的体外和体内生长。我们证明 IE86 蛋白与 ATF5 物理相互作用并乙酰化，从而促进神经胶质瘤细胞存活。因此，我们的研究结果说明了 HCMV 感染在加速神经胶质瘤进展中的生物学意义，并提供了新的证据表明 HCMV 感染可以作为人类神经胶质瘤的治疗靶点。
Human cytomegalovirus (HCMV), a widespread beta-herpes virus, infects a high percentage of gliomas. HCMV is specifically detected in human gliomas at a low level of expression raises the possibility that it may regulate the malignant phenotype in a chronic manner. Although HCMV is not recognized as an oncogenic virus, it might dysregulate signaling pathways involved in initiation and promotion of malignancy. Here, our immunohistochemical staining reveals that nucleus staining of the HCMV 86-kDa immediate-early protein (IE86) is markedly increased in GBM (58.56%) compared with that in nontumorous samples (4.20%) and low-grade glioma(19.56%). IE86 staining positively correlates with the staining of activating transcription factor 5 (ATF5) which is essential for glioma cell viability and proliferation suggesting that HCMV IE86 could have important implications in glioma biology. Moreover, we find that the IE86 overexpression enhances glioma cell's growth in vitro and in vivo. We demonstrate that IE86 protein physically interacts with, and acetylates ATF5 thereby promoting glioma cell survival. Therefore, our findings illustrate the biological significance of HCMV infection in accelerating glioma progression, and provide novel evidence that HCMV infection may serve as a therapeutic target in human glioma.
影响因子：
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作者：
Sheng Z;Evans SK;Green MR
通讯作者：
Green MR