Journal
FEBS LETTERS
Volume 587, Issue 9, Pages 1287-1292Publisher
WILEY
DOI: 10.1016/j.febslet.2013.03.004
Keywords
HBx; Nucleolar stress; p53; MDM2; Drug resistance
Funding
- Council of Scientific and Industrial Research (CSIR), New Delhi [37(1398)/10/EMR-II]
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The nucleolus is a stress sensor associated with cell cycle progression and a viral target. However, the role of the nucleolus during hepatitis B virus infection has not been studied. Here we show that under nucleolar stress, the HBx oncoprotein down-regulates p53 and p21(waf1) levels by disrupting the interaction between ribosomal protein L11 and MDM2. Further, HBx inhibited Act D-mediated down-regulation of proliferative factors such as c-Myc and cyclin E and revived RNA pol I-dependent transcription under these conditions. Importantly, HBx also countered the action of anticancer drug Paclitaxel suggesting its possible role in drug resistance. Thus, HBx not only can facilitate cell proliferation under stress conditions but can confer resistance against anticancer drugs. Structured summary of protein interactions: RPL11 physically interacts with HBx and MDM2 by anti bait coimmunoprecipitation (View interaction) MDM2 physically inter acts with HBx by anti bait coimmunoprecipitation (View interaction) p53 physically interacts with HBx by anti bait coimmunoprecipitation (View interaction) (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
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