國家衛生研究院 NHRI:Item 3990099045/2085
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    題名: Hepatitis B virus pre-S-2 mutant surface antigen induces degradation of cyclin-dependent kinase inhibitor p27(Kip1) through c-Jun activation domain-binding protein 1
    作者: Hsieh, YH;Su, IJ;Wang, HC;Tsai, JH;Huang, YJ;Chang, WW;Lai, MD;Lei, HY;Huang, W
    貢獻者: Division of Clinical Research
    摘要: The hepatitis B virus (HBV) large surface antigen (LHBS) mutant with deletion at the pre-S-2 region accumulates in endoplasmic reticulum (ER) and is associated with HBV-induced hepatocellular carcinogenesis. In this study, we found that the pre-S-2 LHBS mutant directly interacts with the Jun activation domain-binding protein 1 (JAB1). Association of pre-S-2 LHBS with JAB1 dissociated JAB1 from the JAB1/IRE1 complex in ER. The free (active) JAB1 then translocated into cell nuclei and rendered the Cdk inhibitor P27 (KiP1) to cytosolic proteasome for degradation. The pre-S-2 LHBS mutant induced hyperphosphorylation of tumor suppressor retinoblastoma (RB) via cyclin-dependent kinase 2 (Cdk2), a downstream molecule regulated by p27(Kip1). This effect is independent of the ER stress signaling pathway. The transgenic mice carrying the pre-S-2 mutant LHBS gene also exhibited Cdk2 activation, p27(Kip1) degradation, as well as RB hyperphosphorylation. The mouse hepatocytes exhibited morphologic abnormalities such as chromatin condensation, multi nucleation, and dysplasia of hepatocytes. In summary, the pre-S-2 LHBS mutant causes p27(Kip1) degradation through direct interaction with JAB1. The pre-S-2 mutant LHBS is suggested to be a potential oncoprotein for HBV-related hepatocellular carcinoma.
    關鍵詞: Oncology;Cell Biology
    日期: 2007-10
    關聯: Molecular Cancer Research. 2007 Oct;5(10):1063-1072.
    Link to: http://dx.doi.org/10.1158/1541-7786.MCR-07-0098
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1541-7786&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000250474000008
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=35948946094
    顯示於類別:[蘇益仁(2002-2015)] 期刊論文

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