https://scholars.lib.ntu.edu.tw/handle/123456789/560399
標題: | Hepatitis B virus X protein induces IKKα nuclear translocation via Akt-Dependent phosphorylation to promote the motility of hepatocarcinoma cells | 作者: | Huang W.-C. Chen W.-S. Chen Y.-J. Wang L.-Y. Hsu S.-C. CHING-CHOW CHEN Hung M.-C. |
公開日期: | 2012 | 卷: | 227 | 期: | 4 | 起(迄)頁: | 1446-1454 | 來源出版物: | Journal of Cellular Physiology | 摘要: | Hepatitis B virus (HBV) X protein (HBx) has been implicated in HBV-associated carcinogenesis through activation of IκB kinase (IKK)/nuclear factor kappa B (NF-κB) signaling pathway. Besides activating NF-κB in the cytoplasm, IKKα was found in the nucleus to regulate gene expression epigenetically in response to various stimuli. However, it is unknown whether nuclear IKKα plays a role in HBx-associated tumor progression. Moreover, the molecular mechanism underlying IKKα nuclear transport also remains to be elucidated. Here, we disclosed HBx as a new inducer of IKKα nuclear transport in hepatoma cells. HBx induced IKKα nuclear transport in an Akt-dependent manner. HBx-activated Akt promoted IKKα nuclear translocation via phosphorylating its threonine-23 (Thr23). In addition, IKKα ubiquitination enhanced by HBx and Akt also contributed to the IKKα accumulation in the nucleus, indicating the involvement of ubiquitination in Akt-increased IKKα nuclear transport in response to HBx. Furthermore, inhibition of IKKα nuclear translocation by mutation of its nuclear localization signal and Thr23 diminished IKKα-dependent cell migration. Taken together, our findings shed light on the molecular mechanism of IKKα nuclear translocation and provide a potential role of nuclear IKKα in HBx-mediated hepatocellular carcinoma (HCC) progression. ? 2011 Wiley Periodicals, Inc. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/560399 | ISSN: | 219541 | DOI: | 10.1002/jcp.22860 | SDG/關鍵字: | hepatitis B virus X protein; I kappa B kinase alpha; protein kinase B; threonine; article; cancer cell culture; carcinoma cell; cell migration; cell motility; cell nucleus; controlled study; enzyme activation; enzyme inhibition; enzyme phosphorylation; intracellular signaling; intracellular transport; liver carcinogenesis; liver cell carcinoma; priority journal; protein aggregation; protein function; protein localization; ubiquitination; Active Transport, Cell Nucleus; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Movement; Disease Progression; HEK293 Cells; Hep G2 Cells; Hepatitis B virus; Humans; I-kappa B Kinase; Liver Neoplasms; Mutagenesis, Site-Directed; Neoplasm Invasiveness; Nuclear Localization Signals; Phosphorylation; Proto-Oncogene Proteins c-akt; Trans-Activators; Ubiquitination; Viral Proteins; Hepatitis B virus |
顯示於: | 藥理學科所 |
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