The HBx protein of hepatitis B virus confers resistance against nucleolar stress and anti-cancer drug-induced p53 expression

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 p21waf1 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 interactionsRPL11physically interacts withHBx and MDM2 by anti bait coimmunoprecipitation (View interaction)MDM2physically interacts with HBx by anti bait coimmunoprecipitation (View interaction)p53physically interacts with HBx by anti bait coimmunoprecipitation (View interaction)

• HBx down-regulates intracellular levels of p53 and p21waf1 under nucleolar stress.
• HBx disrupts interaction between ribosomal protein L11 and MDM2 under stress.
• HBx inhibits Act D-mediated down-regulation of c-Myc and cyclin E levels.
• HBx also inhibits Act D-mediated down-regulation of rRNA transcripts.
• HBx counters the anticancer activity of Paclitaxel.