{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T04:43:02Z","timestamp":1781152982398,"version":"3.54.1"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,1,11]],"date-time":"2012-01-11T00:00:00Z","timestamp":1326240000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hepatitis B virus (HBV) X protein (HBx) has been implicated in HBV\u2010associated carcinogenesis through activation of I\u03baB kinase (IKK)\/nuclear factor kappa B (NF\u2010\u03baB) signaling pathway. Besides activating NF\u2010\u03baB in the cytoplasm, IKK\u03b1 was found in the nucleus to regulate gene expression epigenetically in response to various stimuli. However, it is unknown whether nuclear IKK\u03b1 plays a role in HBx\u2010associated tumor progression. Moreover, the molecular mechanism underlying IKK\u03b1 nuclear transport also remains to be elucidated. Here, we disclosed HBx as a new inducer of IKK\u03b1 nuclear transport in hepatoma cells. HBx induced IKK\u03b1 nuclear transport in an Akt\u2010dependent manner. HBx\u2010activated Akt promoted IKK\u03b1 nuclear translocation via phosphorylating its threonine\u201023 (Thr23). In addition, IKK\u03b1 ubiquitination enhanced by HBx and Akt also contributed to the IKK\u03b1 accumulation in the nucleus, indicating the involvement of ubiquitination in Akt\u2010increased IKK\u03b1 nuclear transport in response to HBx. Furthermore, inhibition of IKK\u03b1 nuclear translocation by mutation of its nuclear localization signal and Thr23 diminished IKK\u03b1\u2010dependent cell migration. Taken together, our findings shed light on the molecular mechanism of IKK\u03b1 nuclear translocation and provide a potential role of nuclear IKK\u03b1 in HBx\u2010mediated hepatocellular carcinoma (HCC) progression. J. Cell. Physiol. 227: 1446\u20131454, 2012. \u00a9 2011 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jcp.22860","type":"journal-article","created":{"date-parts":[[2011,5,26]],"date-time":"2011-05-26T13:03:18Z","timestamp":1306414998000},"page":"1446-1454","source":"Crossref","is-referenced-by-count":25,"title":["Hepatitis B virus X protein induces IKK\u03b1 nuclear translocation via Akt\u2010Dependent phosphorylation to promote the motility of hepatocarcinoma cells"],"prefix":"10.1002","volume":"227","author":[{"given":"Wei\u2010Chien","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Shu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun\u2010Ju","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010Yun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng\u2010Chieh","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching\u2010Chow","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mien\u2010Chie","family":"Hung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,1,11]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01648"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2005.07.008"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112475200"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403621101"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80595-4"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310686200"},{"key":"e_1_2_5_8_1","first-page":"1059","article-title":"Current status of Akt in non\u2010small cell lung cancer","volume":"13","author":"Chen B","year":"2010","journal-title":"Zhongguo Fei Ai Za Zhi"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1331360100"},{"key":"e_1_2_5_10_1","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1096\/fj.03-1429fje","article-title":"Hepatitis B viral HBx induces matrix metalloproteinase\u20109 gene expression through activation of ERK and PI\u20103K\/AKT pathways: Involvement of invasive potential 3","volume":"18","author":"Chung TW","year":"2004","journal-title":"FASEB J"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0606476104"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600845"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1928"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.3.1452-1461.2006"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.26.2.457-471.2006"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2004.10.010"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0929-6646(09)60051-6"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.02.019"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)00011-1"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200215887"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.1270"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.24.8521-8532.2001"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05656"},{"key":"e_1_2_5_24_1","first-page":"187","article-title":"The pathogenesis of hepatocellular carcinoma is multifactorial event. 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