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Journal article
Novel Autoregulatory Function of Hepatitis B Virus M Protein on Surface Gene Expression
The Journal of biological chemistry, v 280(30), pp 27742-27754
29 Jul 2005
PMID: 15899887
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The hepatitis B virus surface gene consists of a single open reading frame divided into three coding regions: pre-S1, pre-S2, and S. By alternate translation at each of the three initiation codons, L, M, and S proteins can be synthesized. Studies have shown that M protein is not essential for viral replication, virion morphogenesis, or in vitro infectivity. In this study, we show that native M protein can regulate surface gene expression at the transcriptional level. The regulatory effect of M protein is mediated through the CCAAT box within the S promoter. Deletion mapping analysis indicated that the transactivating effect of M protein is mediated through amino acids 1–57 of M protein (the MHBsau domain), although its maximal transactivation activity coincides with that of the pre-S2 domain. This conclusion is supported by the fact that disruption of the putative V8 protease site at the pre-S2/S domain junction not only rendered M protein incapable of transactivating the S promoter but also inactivated its nuclear translocation potential. Immunoprecipitation and immunoblot experiments demonstrated that pre-S2 interacts with the three subunits of the CCAAT box-binding factor/nuclear factor Y, the cognate binding protein of the CCAAT box. These results demonstrate and define a novel regulatory role of M protein, which, under natural conditions, may undergo a proteolytic process to generate an MHBsau species that will be translocated inside the nucleus, where it will interact with the CCAAT box-binding factor to regulate surface gene expression. Because the CCAAT box is located at a fixed position within numerous promoters, these observations might provide a plausible explanation for hepatitis B virus-associated hepatocarcinogenesis.
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Details
- Title
- Novel Autoregulatory Function of Hepatitis B Virus M Protein on Surface Gene Expression
- Creators
- Tsurng-Juhn Huang - Institute of Basic Medical SciencesCheng-Chan Lu - Institute of Basic Medical SciencesJui-Chen Tsai - National Cheng Kung UniversityWei-Jen Yao - Departments of Nuclear MedicineXuanyong Lu - National Cheng Kung UniversityMing-Derg Lai - Institute of Basic Medical SciencesHsiao-Sheng Liu - Institute of Basic Medical SciencesAi-Li Shiau - Institute of Basic Medical Sciences
- Publication Details
- The Journal of biological chemistry, v 280(30), pp 27742-27754
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000230678600033
- Scopus ID
- 2-s2.0-23044439041
- Other Identifier
- 991019173444704721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology