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Study for mechanisms of NF-κB activation by hepatitis C viral core protein

Research Project

Project/Area Number 13670296
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

HIJIKATA Makoto  Inst. Virus. Res., Kyoto Univ., Assoc. Prof., ウイルス研究所, 助教授 (90202275)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥2,300,000 (Direct Cost: ¥2,300,000)
Keywordshapatitis C virus / chronic infection / NF-κB / retinoic acid / transcriptional cofactor / Sp110b / replicon / 肝癌 / Two Hybrid / タンパク質間相互作用 / レチノイン酸レセプター / 転写コファクター / ゲノム複製 / Two Hybrid法
Research Abstract

Chronic infection of hepatitis C virus (HCV) is considered to cause the development of chronic hepatitis, liver cirrohsis, and hepatocellular carcinoma. We tried, therefore, to reveal the molecular mechanism of NF-κB activation by the HCV core protein (the core) which has been suggested to be related with the persistent infection of this virus. Using the yeast two hybrid screening system, we obtained several candidates of cellular factors interacting with the core. One of the candidates was Sp110b, which was reported to be a splicing variant of Sp110, a transcriptional cofactor of retinoic acid receptor (RAR). As we observed that the core enhanced the transcriptional activity of RAR, finer analyses for the relationship between the core and Sp110b were performed. Expression level of Sp110b mRNA was higher than that of Sp110. We also observed that overproduction of Sp110b suppressed the RAR-dependent transcriptional activation, suggesting that Sp110b is a negative cofactor of RAR-dependent transcription. We found that the subcellular localization of Sp110b which was originally located in the nucleus was changed to the perinuclear cytoplasmic region, when the core was coproduced in the cells. That change as well as the enhancement of RAR-dependent transcriptional activation was reverted by the coproduction of minimum region of Sp110b required for binding with the core, suggesting that the interaction between the core and Sp110b is important for those phenomenons. As a transcriptional cofactor has been revealed to be related with several transcriptional events, we now examine the contribution of Sp110b to the activation of NF-κB by the core.
Furthermore, we have established the cell line in which HCV genomic replicon including whole HCV genome was replicated and maintained in order to examine the effect of the core in such cells. The analysis of function of Sp110b on the HCV genome replication is underway by using this cell line.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Marusawa H, et al.: "Regulation of Fas-mediated apoptosis by NF-kappaB activity in human hepatocyte derived cell lines"Microbiol Immunol. 45. 483-489 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watashi K, et al.: "Cytoplasmic localization is important for transcription factor nuclear factor-kappa B activation by hepatitis C virus core protein through its amino terminal region"Virology. 286. 391-402 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fukuda K, et al.: "Hepatitis C virus core protein enhances the activation of the transcription factor, Elk1, in response to mitogenic stimuli"Hepatology. 33. 159-165 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kishine H., et al.: "Subgenomic replicon derived from a cell line infected with the hepatitis C virus"Biochem. Biophys. Res. Commun.. 293. 993-999 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimotohno K., et al.: "Hepatitis C virus and its roles in cell proliferation"J. Gastroenterol.. 37. 50-54 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Marusawa H, Hijikata M, Watashi K, Chiba T, Shimotohno K: "Regulation of Fas-mediated apoptosis by NF-kappaB activity in human hepatocyte derived cell lines"Microbiol Immunol. 45. 483-489 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watashi K, Hijikata M, Marusawa H, Doi T, Shimotohno K: "Cytoplasmic localization is important for transcription factor nuclear factor-kappa B activation by hepatitis C virus core protein through its amino terminal region"Virology. 286. 391-402 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fukuda K, Tsuchihara K, Hijikata M, Nishiguchi S, Kuroki T, Shimotohno K: "Hepatitis C virus core protein enhances the activation of the transcription factor, Elk1, in response to mitogenic stimuli"Hepatology. 33. 159-165 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kishine H., Sugiyama K., Hijikata M., Kato N., Takahashi H., Noshi T., Nio Y., Hosaka M., Miyanari Y., Shimotohno K.: "Subgenomic replicon derived from a cell line infected with the hepatitis C virus"Biochem. Biophys. Res. Commun.. 293. 993-999 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimotohno K., Watashi K., Tsuchihara K, Marusawa H., Fukuda K., Hijikata M.: "Hepatitis C virus and its roles in cell proliferation"J. Gastroenterol.. 37. 50-54 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Kishine, et al.: "Subgenomic replicon derived from a cell line infected with the hepatitis C virus"Biochem. Biophys. Res. Commun.. 293・3. 993-999 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Shimotohno, et al.: "Hepatitis C virus and its roles in cell proliferation"J. Gastroenterol.. 37・sup13. 50-54 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Noguchi, et al.: "Effects of mutation in hepatitis C virus nonstructural protein 5A on Interferon resistance mediated by inhibition of PKR kinaseactivityinmammalian cells"Microbiology and Immunol. ogy. 45・12. 829-840 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] H.Marusawa, et al.: "Regulation of Fas-mediated apoptosis by NF-kappaB activity in human hepatocyte derived cell lines"Microbiology and Immunol. ogy. 45・6. 483-489 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Watashi, et al.: "Cytoplasmic localization is important for transcription factor nuclear factor-kappaB activation by hepatitis C virus core protein through its amino terminal region"Virology. 286・2. 391-402 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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