Calcium Signaling by HBx Protein in Hepatitis B Virus DNA Replication
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- 14 December 2001
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 294 (5550), 2376-2378
- https://doi.org/10.1126/science.294.5550.2376
Abstract
Hepatitis B virus (HBV) infects more than 300 million people and is a leading cause of liver cancer and disease. The HBV HBx protein is essential for infection; HBx activation of Src is important for HBV DNA replication. In our study, HBx activated cytosolic calcium-dependent proline-rich tyrosine kinase–2 (Pyk2), a Src kinase activator. HBx activation of HBV DNA replication was blocked by inhibiting Pyk2 or calcium signaling mediated by mitochondrial calcium channels, which suggests that HBx targets mitochondrial calcium regulation. Reagents that increased cytosolic calcium substituted for HBx protein in HBV DNA replication. Thus, alteration of cytosolic calcium was a fundamental requirement for HBV replication and was mediated by HBx protein.Keywords
This publication has 26 references indexed in Scilit:
- Hepatitis B Virus (HBV) Virion and Covalently Closed Circular DNA Formation in Primary Tupaia Hepatocytes and Human Hepatoma Cell Lines upon HBV Genome Transduction with Replication-Defective Adenovirus VectorsJournal of Virology, 2001
- Association of hepatitis B virus X protein with mitochondria causes mitochondrial aggregation at the nuclear periphery, leading to cell deathOncogene, 1999
- The hepatitis B virus X protein activates nuclear factor of activated T cells (NF-AT) by a cyclosporin A-sensitive pathwayThe EMBO Journal, 1998
- Identification of an ion channel activity of the Vpu transmembrane domain and its involvement in the regulation of virus release from HIV‐1‐infected cellsFEBS Letters, 1996
- A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activationNature, 1996
- Protein tyrosine kinase PYK2 involved in Ca2+-induced regulation of ion channel and MAP kinase functionsNature, 1995
- The hepatitis B virus X protein targets the basic region-leucine zipper domain of CREB.Proceedings of the National Academy of Sciences, 1995
- Calcium signalingCell, 1995
- Hepatitis B virus HBx protein activates Ras-GTP complex formation and establishes a Ras, Raf, MAP kinase signaling cascade.Proceedings of the National Academy of Sciences, 1994
- HBV X Protein Alters the DNA Binding Specificity of CREB and ATF-2 by Protein-Protein InteractionsScience, 1991