2007 Fiscal Year Final Research Report Summary
Effects of hepatitis C virus proteins on protein-tyrosine phosphorylation in liver cells
| Project/Area Number |
18590293
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | University of Fukui |
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Principal Investigator |
SADA Kiyonao University of Fukui, Faculty of Medical Sciences, Professor (10273765)
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| Co-Investigator(Kenkyū-buntansha) |
HOTTA Haku Kobe University, Graduate School of Medicine, Professor (40116249)
NAGANO-FUJII Motoko Kobe University, Graduate School of Medicine, Assistant Professor (90304089)
HATANI Tomoko University of Fukui, Faculty of Medical Sciences, Assistant Professor (60452124)
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| Project Period (FY) |
2006 – 2007
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| Keywords | hepatitis C virus / protein-tvrosine phosphorylation / protein-tyrosine kinase / virus-host relationship / signal transduction / Svk / proteome analysis |
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| Research Abstract |
The aim of this study is to investigate the effects of hepatitis C virus (HCV) proteins on protein-tyrosine phosphorylation, in particular, protein-tyrosine kinase Syk in vivo.
In 2006, we identified that HCV non-structural protein 5A (NS5A) strongly interacted with Syk, and phospholipase C (PLC)-γ1 was the intracellular target of Syk in cultured liver cells (Huh-7 cells). Moreover, we investigated the pathological mechanism of HCV NS3 and NS4A, identification of novel SSPE virus, and characterization of virus-related ubiquitin ligase, and reported their results.
In 2007, we found that interaction of NS5A with Syk was detected also in Huh-7.5 cells harboring an HCV RNA replicon and those infected with HCV (HCV J6/JFH-1). Deletion mutational analysis revealed that an N-terminal portion of NS5A was involved in the physical interaction with Syk. In vitro kinase assay demonstrated that NS5A inhibited enzymatic activity of Syk and that, in addition to the N-terminal 175 residues, a central portion of NS5A was required for the Syk inhibition. Moreover, immunohistochemical analysis revealed that endogenous Syk, which otherwise was expressed diffusely in the cytoplasm of normal hepatocytes, was localized near the cell membrane with a patched pattern in HCV-infected hepatocytes. Our results imply the possibility that NS5A is involved in the carcinogenesis of hepatocytes through the suppression of Syk, a potent tumor suppressor in human breast carcinoma. Furthermore, we investigated the pathogenesis of diabetes as a HCV complication and proteome analysis of HCV infection. Furthermore, we examined the role of novel adaptor protein 3BP2 and human inherited disease cherubism and published a review article.
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Research Products
(34 results)
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[Journal Article] A novel mitochondria ubiquitin ligase plays a critical role in mitochondria] dynamics2006
Author(s)
Yonashiro, R., Ishido, S., Kyo, S., Fukuda, T., Goto, E., Matsuki, Y., Ohmura-Hashimoto, M., Sada. K., Hotta, H., Yamamura, H., Inatome, R., Yanagi, S
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Journal Title
EMBO J 25(15)
Pages: 3618-3626
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Full-length sequence analysis of subacute sclerosing panencephalitis (SSPE) virus, a mutant of measles virus, isolated from brain tissues of a patient shortly after onset of SSPE2006
Author(s)
Hotta, H., Nihei, K., Abe, Y., Kato, S., Jiang D. P., Nagano-Fujii, M., Sada, K
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Journal Title
Microbiol. Immunol 50(7)
Pages: 525-534
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The nonstructural protein 4A of hepatitis C virus accumulates on mitochondria and induces apoptotic cell death through a mitochondria-mediated pathway2006
Author(s)
Nomura-Takigawa, Y., Nagano-Fujii, M., Deng, L., Kitazawa, S., Ishido, S., Sada, K., Hotta, H
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Journal Title
J. Gen. Virol 87(7)
Pages: 1935-1945
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The NS3 protein of hepatitis C virus associates with the tumor suppressor p53 and inhibits its function in an NS3 sequence-dependent manner2006
Author(s)
Deng, L., Nagano-Fujii, M., Tanaka, M., Nomura-Takigawa, Y., Ikeda, M., Kato, N., Sada. K., Hotta, H
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Journal Title
J. Gen. Virol 87(6)
Pages: 1703-1713
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Single-point mutations of hepatitis C virus NS3 that impair p53 interaction and anti-apoptotic activity of NS32006
Author(s)
Tanaka, M., Nagano-Fujii, M., Deng, L., Ishido, S., Sada, K., Hotta, H
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Journal Title
Biochem. Biophys. Res. Commun 340(3)
Pages: 792-799
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Hepatitis C virus NS5A protein interacts with and negatively regulates the non-receptor protein-tyrosine kinase Syk
Author(s)
Inubushi, S., Nagano-Fujii, M., Kitayama, K., Tanaka, M., An, C., Yokozaki, H., Yamamura, H., Nuriya, H., Kohara, M., Sada, K., Hotta, H
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Glucose uptake and GLUTI/2 expression are down -regulated in Huh-7.5 cells harboring an HCV subgenomic RNA replicon and full-genomic RNA replicon2007
Author(s)
Kasai, D., Nagano-Fujii, M., Bungyoku, Y., Sasayama, M., Sada. K., Hotta, H
Organizer
14th International Symposium on Hepatitis Virus and Related Viruses
Place of Presentation
Glasgow, UK
Year and Date
2007-09-10
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Kinase activity of the non-receptor tyrosine kinase Syk is down-regulated in Huh-7.5 cells harboring an HCV RNA subgenomic replicon2006
Author(s)
Inubushi, S., Nagano-Fujii, M., Kitayama, K., Yamamura, H., Sada, K., Hotta, H
Organizer
13th International Symposium on Hepatitis C Virus and Related Viruses
Place of Presentation
Sydney, Australia
Year and Date
2006-08-28
Description
「研究成果報告書概要(欧文)」より
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[Presentation] A high degree of sequence variation of HCV NS5A and the presence of anti-NS5A antibodies in the pretreatment sera are associated with efficient viral clearance by combination therapy using pegylated interferon and ribavirin2006
Author(s)
El-Shamy, A., Sasayama, M., Nagano-Fujii, M., Sada, K., Kim, S. R., Hotta, H
Organizer
13th International Symposium on Hepatitis C Virus and Related Viruses
Place of Presentation
Sydney, Australia
Year and Date
2006-08-28
Description
「研究成果報告書概要(欧文)」より
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