Hepatitis B virus X protein induces IKKa nuclear translocation via Akt-Dependent phosphorylation to promote the motility of hepatocarcinoma cells
Hepatitis B virus X protein induces IKKa nuclear translocation via Akt-Dependent phosphorylation to promote the motility of hepatocarcinoma cells
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DOI：
10.1002/jcp.22860
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发表时间：
2012-04-01
影响因子：
5.6
通讯作者：
Hung, Mien-Chie
中科院分区：
文献类型：
--
作者：
Huang, Wei-Chien;Chen, Wen-Shu;Hung, Mien-Chie
乙型肝炎病毒（HBV） X蛋白（HBx）通过激活I？B激酶(IKK)/核因子B (NF-？B)信号通路。除了激活NF-？在细胞质中发现IKKa，在细胞核中发现IKKa以表观遗传方式调节基因表达，以响应各种刺激。然而，核IKKa是否在hbx相关的肿瘤进展中起作用尚不清楚。此外，IKKa核转运的分子机制也有待阐明。在这里，我们发现HBx是肝癌细胞中IKKa核转运的新诱导剂。HBx以akt依赖的方式诱导IKKa核转运。hbx激活的Akt通过磷酸化其苏氨酸-23 （Thr23）促进IKKa核易位。此外，HBx和Akt增强的IKKa泛素化也促进了IKKa在细胞核中的积累，这表明泛素化参与了HBx作用下Akt增加的IKKa核转运。此外，通过IKKa核定位信号和Thr23的突变抑制IKKa核易位可以减少IKKa依赖性细胞的迁移。综上所述，我们的研究结果揭示了IKKa核易位的分子机制，并提供了核IKKa在hbx介导的肝细胞癌（HCC）进展中的潜在作用。j .细胞。中国生物医学工程学报，2016,31(2):444 - 444。(C) 2011 Wiley期刊公司
Hepatitis B virus (HBV) X protein (HBx) has been implicated in HBV-associated carcinogenesis through activation of I?B kinase (IKK)/nuclear factor kappa B (NF-?B) signaling pathway. Besides activating NF-?B in the cytoplasm, IKKa was found in the nucleus to regulate gene expression epigenetically in response to various stimuli. However, it is unknown whether nuclear IKKa plays a role in HBx-associated tumor progression. Moreover, the molecular mechanism underlying IKKa nuclear transport also remains to be elucidated. Here, we disclosed HBx as a new inducer of IKKa nuclear transport in hepatoma cells. HBx induced IKKa nuclear transport in an Akt-dependent manner. HBx-activated Akt promoted IKKa nuclear translocation via phosphorylating its threonine-23 (Thr23). In addition, IKKa ubiquitination enhanced by HBx and Akt also contributed to the IKKa accumulation in the nucleus, indicating the involvement of ubiquitination in Akt-increased IKKa nuclear transport in response to HBx. Furthermore, inhibition of IKKa nuclear translocation by mutation of its nuclear localization signal and Thr23 diminished IKKa-dependent cell migration. Taken together, our findings shed light on the molecular mechanism of IKKa nuclear translocation and provide a potential role of nuclear IKKa in HBx-mediated hepatocellular carcinoma (HCC) progression. J. Cell. Physiol. 227: 1446-1454, 2012. (C) 2011 Wiley Periodicals, Inc.