title: Hepatitis B virus X protein induces IKKα nuclear translocation via Akt-dependent phosphorylation to promote the motility of hepatocarcinoma cells.
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.
authors: Graduate Institute of Cancer Biology, China Medical University and Hospital, Taichung, Taiwan. whuang@mail.cmu.edu.tw
authors: Wei-Chien
authors: WC
authors: Huang
authors: Wen-Shu
authors: WS
authors: Chen
authors: Yun-Ju
authors: YJ
authors: Chen
authors: Li-Yun
authors: LY
authors: Wang
authors: Sheng-Chieh
authors: SC
authors: Hsu
authors: Ching-Chow
authors: CC
authors: Chen
authors: Mien-Chie
authors: MC
authors: Hung