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Hepatitis B virus X protein induces IKKα nuclear translocation via Akt‐Dependent phosphorylation to promote the motility of hepatocarcinoma cells
Author(s) -
Huang WeiChien,
Chen WenShu,
Chen YunJu,
Wang LiYun,
Hsu ShengChieh,
Chen ChingChow,
Hung MienChie
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22860
Subject(s) - hbx , iκb kinase , protein kinase b , phosphorylation , nuclear export signal , nuclear transport , biology , cancer research , pi3k/akt/mtor pathway , signal transduction , microbiology and biotechnology , nuclear localization sequence , cell nucleus , chemistry , nf κb , cytoplasm , hepatitis b virus , immunology , virus
Abstract 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. J. Cell. Physiol. 227: 1446–1454, 2012. © 2011 Wiley Periodicals, Inc.