| Project/Area Number |
16590385
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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 |
Virology
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| Research Institution | Osaka University |
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Principal Investigator |
MORIISHI Kohji Osaka University, Research Institute for Microbial Diseases, Associate professor, 微生物病研究所, 助教授 (90260273)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Hepatitis C / HCV core protein / Hepatitis C virus / Proteasome / PA28γ / Signal peptide peptidase |
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| Research Abstract |
The third place of cancer death in our country is liver cancer, of which eighty percentage patients are infected with hepatitis C virus (HCV). HCV core protein is well known to be the capsid protein as well as the pathogenic factor, because liver cancer and steatosis are found in HCV core protein-transgenic mouse. The aims of our study are to clarify the mechanism by which HCV core protein induces pathogenicity and to understand how HCV core protein is processed by host protein.
1)Effect of PA28gamma on processing and pathogenicity of HCV core protein.
Expression of PA28gamma was suppressed by short hairpin-typed RNA under the control of U6 promoter. Posttranslational and translational modifications of the proteins related to cell growth and lipid biosynthesis in PA28gamma-knockdown cells were different from those in parents cells. We also determine the region spanning from residues 139 to 144 as the essential domain for ER retention and the region from residues 176 to 177 as the SPP-processing essential region. In addition, our data also suggest that oligomerization of HCV core protein is important for E1 interaction.
2)Biological function of HCV core protein is regulated by SPP and PA28gamma
C-terminal transmembrane region of HCV core protein is processed by signal peptidase and then signal peptide peptidase. Analysis of MALDI-TOF/MS suggests that C-terminal amino acid residue is determined as residue 178. Our data also suggest that SPP processing affects intracellular localization of HCV core protein and that HCV core protein regulates the nuclear proteasome activity.
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