RPS27a enhances EBV-encoded LMP1-mediated proliferation and invasion by stabilizing of LMP1
RPS27a enhances EBV-encoded LMP1-mediated proliferation and invasion by stabilizing of LMP1
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DOI：
10.1016/j.bbrc.2017.07.105
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发表时间：
2017-09-16
影响因子：
3.1
通讯作者：
Hur, Dae Young
中科院分区：
文献类型：
--
作者：
Hong, Seung-Woo;Kim, Seung-Mi;Hur, Dae Young
EB病毒编码的潜伏膜蛋白1(LMP1)是一种在EBV诱导的肿瘤转化中起关键作用的肿瘤病毒蛋白。LMP1在EB病毒诱导的肿瘤发生中的作用已经得到了很好的研究。然而，LMP1蛋白稳定性背后的分子机制仍然知之甚少。在本研究中，我们通过串联亲和纯化分析发现，核糖体蛋白s27a(RPS27a)调节LMP1的稳定性。RPS27a在体内外与LMP1直接相互作用。此外，在293T细胞中过表达RPS27a延长了LMP1的半衰期，而利用慢病毒shRNA技术下调RPS27a则加速了EBV转化的B细胞中LMP1蛋白水平的下降。我们发现，通过蛋白酶体的LMP1泛素化完全被RPS27a的过度表达所抑制。RPS27a还促进LMP1介导的增殖和侵袭，提示RPS27a与LMP1相互作用，并通过抑制蛋白酶体介导的泛素化来稳定LMP1。这些结果表明，RSP27a可能是EBV感染的LMP1阳性癌细胞的潜在靶点。(C)2017 Elsevier Inc.保留所有权利。
Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is an oncoviral protein that plays a pivotal role in EBV-induced oncogenic transformation. The function of LMP1 in EBV-induced oncogenesis has been well studied. However, the molecular mechanisms underlying LMP1 protein stability remain poorly understood. In this study, we found that ribosomal protein s27a (RPS27a) regulates LMP1 stability by a tandem affinity purification analysis. RPS27a interacts directly with LMP1 in vitro and in vivo. Furthermore, overexpression of RPS27a increases the half-life of LMP1 in 293T cells, whereas down regulation of RPS27a using lentiviral shRNA technology accelerates the decrease in LMP1 protein level in EBV-transformed B cells. We show that LMP1 ubiquitination via the proteasome is completely inhibited by overexpression of RPS27a. RPS27a also enhances LMP1-mediated proliferation and invasion, suggesting that RPS27a interacts with LMP1 and stabilizes it by suppressing proteasome-mediated ubiquitination. These results suggest that RSP27a could be a potential target in EBV-infected LMP1-positive cancer cells. (C) 2017 Elsevier Inc. All rights reserved.