The HBx protein of hepatitis B virus confers resistance against nucleolar stress and anti-cancer drug-induced p53 expression
The HBx protein of hepatitis B virus confers resistance against nucleolar stress and anti-cancer drug-induced p53 expression
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DOI：
10.1016/j.febslet.2013.03.004
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发表时间：
2013-05-02
期刊：
影响因子：
3.5
通讯作者：
Kumar, Vijay
中科院分区：
文献类型：
--
作者：
Kapoor, Neetu Rohit;Ahuja, Richa;Kumar, Vijay
核仁是与细胞周期进展相关的压力传感器和病毒靶点。然而，核仁在B型肝炎病毒感染过程中的作用尚未研究。在这里，我们表明，在核仁压力下，HBx癌蛋白下调p53和p21（waf 1）的水平，通过破坏核糖体蛋白L11和MDM 2之间的相互作用。此外，HBx抑制Act D介导的增殖因子如c-Myc和细胞周期蛋白E的下调，并在这些条件下恢复RNA pol I依赖性转录。重要的是，HBx还对抗抗癌药物Paclitaxel的作用，表明其在耐药性中的可能作用。因此，HBx不仅可以促进细胞在应激条件下的增殖，而且可以赋予抗癌药物的抗性。蛋白质相互作用的结构总结：RPL 11通过抗诱饵免疫共沉淀与HBx和MDM 2物理相互作用MDM 2通过抗诱饵免疫共沉淀与HBx发生物理相互作用（查看相互作用）p53通过抗诱饵免疫共沉淀与HBx物理相互作用（查看相互作用）（C）2013欧洲生物化学学会联合会。由Elsevier B出版。V.保留所有权利。
The nucleolus is a stress sensor associated with cell cycle progression and a viral target. However, the role of the nucleolus during hepatitis B virus infection has not been studied. Here we show that under nucleolar stress, the HBx oncoprotein down-regulates p53 and p21(waf1) levels by disrupting the interaction between ribosomal protein L11 and MDM2. Further, HBx inhibited Act D-mediated down-regulation of proliferative factors such as c-Myc and cyclin E and revived RNA pol I-dependent transcription under these conditions. Importantly, HBx also countered the action of anticancer drug Paclitaxel suggesting its possible role in drug resistance. Thus, HBx not only can facilitate cell proliferation under stress conditions but can confer resistance against anticancer drugs.Structured summary of protein interactions: RPL11 physically interacts with HBx and MDM2 by anti bait coimmunoprecipitation (View interaction) MDM2 physically inter acts with HBx by anti bait coimmunoprecipitation (View interaction)p53 physically interacts with HBx by anti bait coimmunoprecipitation (View interaction) (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.