title: The HBx protein of hepatitis B virus confers resistance against nucleolar stress and anti-cancer drug-induced p53 expression.
abstract: 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.
authors.affiliation: Virology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Neetu Rohit
authors.initials: NR
authors.lastname: Kapoor
authors.forename: Richa
authors.initials: R
authors.lastname: Ahuja
authors.forename: Surendra K
authors.initials: SK
authors.lastname: Shukla
authors.forename: Vijay
authors.initials: V
authors.lastname: Kumar
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002466:Cell Nucleolus / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology; D055550:Protein Stability; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012318:RNA Polymerase I; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013312:Stress, Physiological / Q000187:drug effects; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D000970:Antineoplastic Agents; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D012269:Ribosomal Proteins; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D051736:Proto-Oncogene Proteins c-mdm2; D012318:RNA Polymerase I; D017239:Paclitaxel