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Title 

Reactivation of p53 in cells expressing hepatitis B virus X-protein involves p53 phosphorylation and a reduction of Hdm2

Authors 

J H WangC YunS KimS ChaeYoung Ik LeeW H KimJ H LeeW KimH Cho

Publisher 

Wiley-Blackwell

Issue Date 

2008

Citation 

Cancer Science, vol. 99, no. 5, pp. 888-893

Keywords 

doxorubicinhepatitis B virus X proteinmessenger RNAprotein MDM2protein p53MDM2 protein, humantransactivator proteincell nucleuscytoplasmgene expression

Abstract 

Multifunctional activities of the hepatitis B virus X-protein (HBx) in cells have been largely implicated in the development of liver cancer; one of these activities is the loss of p53 function by sequestering p53 in the cytoplasm. We have previously found that doxorubicin increased the p53 levels in cells containing p53-binding HBx protein and restored the p53-mediated transcriptional activity that was suppressed by HBx. Here, we investigated the mechanism underlying p53 reactivation. We found that six phosphorylation sites of the Serine residues of p53 were efficiently phosphorylated in HBx-expressing ChangX-34 cells, suggesting that the binding of HBx to the p53 protein does not interfere with the phosphorylation of p53 by signaling kinases. In addition, doxorubicin caused a dramatic reduction of Hdm2 mRNA and protein levels in cells expressing HBx. Intriguingly, reactivation of p53 was accompanied with a nuclear accumulation of p53 and the phosphorylated p53 at Serine15 was only detected in nuclear fraction, but not in cytosolic fraction of doxorubicin-treated ChangX-34 cells. Functional restoration of the p53 protein in HBx-expressing cells occurs according to the dual effects of doxorubicin: a significant reduction of Hdm2 expression and a nuclear accumulation of the phosphorylated p53 protein. Thus, proper usage of doxorubicin as an effective antitumor agent may be reevaluated and can be extended to tumors primarily caused by infection of DNA tumor viruses.

ISSN 

1347-9032

Link 

http://dx.doi.org/10.1111/j.1349-7006.2008.00754.x

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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