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2007 Fiscal Year Final Research Report Summary

Subcellular localization and control of activity of telomerase

Research Project

Project/Area Number 17390091
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionKanazawa University

Principal Investigator

MURAKAMI Seishi  Kanazawa University, Cancer Research Institute, Emeritus Professor (90019878)

Co-Investigator(Kenkyū-buntansha) YOSHIOKA Katsuji  Kanazawa University, Cancer Research Institute, Professor (60200937)
HONDA Masao  Kanazawa University, Graduate Course of Medical Science, Professor (00272980)
Project Period (FY) 2005 – 2007
KeywordsCancer / Virus / Protein / Development and Differentiation / Sienal transduction / Telomerase / Nucleolin / Subcellular localization
Research Abstract

Since telomerase activity is barely detectable in primary cells but clearly detected in cancerous cells, telomerase has been considered to be a strong candidate of the targets to cancer treatment In the fiscal year, we concentrated in several experiments including purification and characterization of recombinant human telomerase complex, and biological function of the specific interaction of nucleolin and hTERT recovered from a HeLa cell line stably expressing FLAG-hTERT (Murakami), analyses of human primary cells immortalized by hTERT (Honda), and the tyrosine kinases of receptor type which play critical odes in cell proliferation and differentiation (Yoshioka). The followings are the main conclusions of the experiments.
1) The partially purified active telomerase complexes comprise two different complexities, complex I (around 680 kDa), and complex II (around 400 kDa), that are quite alike to those that can be recovered firm the insect cells co-expressing FLAG-hTERT and hTERC. The com … More plex I does not contain Hsp90 and is resistant to Hsp90 inhibitors, whereas complex II contains Hsp90 and is sensitive to Hsp90 inhibitors. Human TEAT in the complex II is rather unstable during incubation in vim and in ring. Such unstable property was not observed with the complex I. Since MG132, a specific proteasome inhibitor, but not MG133, a negative control, stabilized hTERT in the complex Z strongly suggesting that hTERT in the complex If is under degradation pathway under the control of proteasome. The two different complexities of human telomerase seem to imply two different entities of active telomerase in different subcellular localization or its different functions. 2) We have established a cell line of the human primary fibroblasts(BJ cells) stably expressing hTERT, and we compared expression profiles of RI cells and the KJ cells immortalized by MERE Some genes involving in cell cycle progression and cell proliferation were evidently expressed higher in the immortalized 131-hTERT than these in in the primary cells. 3) Nucleolin, one of the specific interacting partners of hTERT can bind to Hepatitis C Virus (HCV) NS5B, RNA-dependent RNA replication of HCV. We evaluated the role of the specific interaction of nucleolin and NS5B in HCV replication. The HCV subreplicon system has been applied for the address We found that the HCV subreplicons harboring alanine substitution mutations or mutation at the residue(s) either one of two critical sequences within NS5B both of which are necessary for the nucleolin-binding could not replicate at all in a transient HCV replication system in HepG2 ml/s., although the wild replicon could support efficient HCV. By introducing transiently RNAi of nucleolin, that down regulated expression of nucleolin by half to one third, reduced HCV evidently reduced HCV replication using the HCV subreplicon system. Taken together, the specific interaction of nucleolin and NS5B is critical for HCV replication. Less

  • Research Products

    (31 results)

All 2008 2007 Other

All Journal Article (17 results) (of which Peer Reviewed: 9 results) Presentation (14 results)

  • [Journal Article] Hepatitis B Virus X protein overcomes oncogenic RAS-induced senescence in human immortalized cells.2007

    • Author(s)
      Oishi N, Shilagardi K, Nakamoto Y, Honda M, Kaneko S, Murakami S.
    • Journal Title

      Cancer Science 98(10)

      Pages: 1540-1548

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Functional interaction of Hepatitis C Virus(HCV)NS5B with Nucleolin GAR domain.2007

    • Author(s)
      Mizuno H, Shilagazdi K, Seki T, Hirota Y, Kaneko S, *^Murakamki S.
    • Journal Title

      J. Biochem(Tokyo). 98(5)

      Pages: 641-652

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Human telomerase exists in two distinct active complexes in vivo.2007

    • Author(s)
      Kusakawa T, Shimakami T, Kaneko S, Yoshioka K, *^Murakami S.
    • Journal Title

      J. Biochem(Tokyo). 98(10)

      Pages: 917-927

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Mutations in Ran system affected telomere silencing in Saccharomyces cerevisiae2007

    • Author(s)
      Hayashi N, Kobayashi M, Shimizu H Yamamoto K, Murakami S, Nishimoto T.
    • Journal Title

      Biochem Biophys Res Commun. 363(3)

      Pages: 788-794

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Neural-specific ablation of the scaffold protein JSAP1 in mice causes neonatal death.2007

    • Author(s)
      Iwanaga A, Yoshioka K., et. al.
    • Journal Title

      Neurosci. Lett. 429(1)

      Pages: 43-48

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Regulation of N-cadherin-based cell-cell interaction by JSAP1 scaffold in PC12h cells.2007

    • Author(s)
      Bayarsaikhan M, Takino T, Gantulga D, Sato H, Ito T, Yoshioka K.
    • Journal Title

      Biochem. Biophys. Res. Commun. 353(2)

      Pages: 357-362

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Comparative proteomic and transcriptomic profiling of the human hepatocellular carcinoma.2007

    • Author(s)
      Minagawa H, Honda M, Kaneko S., et. al.
    • Journal Title

      Biochem Biophys Res Commun. 366(1)

      Pages: 186-192

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Lipid-induced oxidative stress causes steatohepatitis in mice fed an atherogenicdiet.2007

    • Author(s)
      Matsuzawa N, Honda M, Kaneko S., et. al.
    • Journal Title

      Hepatology 46(5)

      Pages: 1392-1403

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Expression profiling of peripheral-blood mononuclear cells from patients with chronic hepatitis C undergoing interferon therapy.2007

    • Author(s)
      Tateno M, Honda M. Kaneko S., et. al.
    • Journal Title

      J Infect Dis. 195(2)

      Pages: 255-267

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Temperature-sensitive defects of the GSPlgene, yeast Ran homologue, activate the Tell-dependent pathway2007

    • Author(s)
      Hayashi, N., Tsurusaki, S., Nagaura, Z., Oki, M., Nishitani, H., Kobayashi, M., Shimizu, H., Yamamoto, K., Nishimoto, T
    • Journal Title

      Biochem Biophys Res Commun 353(2)

      Pages: 330-336

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Human telomerase exists in two distinct active complexes in vivo2007

    • Author(s)
      Mizuno, H., Khurts, S., Seki, T., Hirota, Y., Kaneko, S., *Murakamk, S
    • Journal Title

      J. Biochem (Tokyo) 141(5)

      Pages: 641-652

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Functional interaction of Hepatitis C Virus (HCV) NS5B with Nucleolin GAR domain2007

    • Author(s)
      Kusakawa, T., Shimakami, T., Kaneko, S., Yoshioka, K., *Mmakami, S
    • Journal Title

      J. Biochem (Tokyo) 141(6)

      Pages: 917-927

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Hepatitis B Virus X protein overcomes oncogenic RAS-induced senescence in human immortalized cells2007

    • Author(s)
      Oishi, N., Khurts, S., Nakamoto, Y., Honda, M., Kaneko, S., *Murakami, S
    • Journal Title

      Cancer Science 98(10)

      Pages: 1540-1548

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Mutations in Ran system affected telomere silencing in Saccharomyces cerevisiae2007

    • Author(s)
      Hayashi, N., Kobayashi, M., Shimizu, H., Yamamoto, K., Murakami, C., Nishimoto, T
    • Journal Title

      Biochem Biophys Res Commun 363(3)

      Pages: 788-794

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Regulation of N-cadherin-based cell-cell interaction by JSAPI scaffold in PC12h cells2007

    • Author(s)
      Bayarsaikhan, M., Takino, T., Gantulga, D., Sato, H., Ito, T., Yoshioka, K
    • Journal Title

      Biochem Biophys Res Commun 353(2)

      Pages: 357-362

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Essential role for class 11 phosphoinositide 3-kinase alpha-isoform in Ca<2+>-induced, Rho- and Rho kinase-dependent regulation of myosin phosphatase and contraction in isolated vascular smooth muscle cells.2007

    • Author(s)
      Yoshioka, K., Sugimoto, N., Takuwa, N., Takuwa, Y
    • Journal Title

      Mol Pharmacol 71(3)

      Pages: 912-920

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Matsuzawa-Nagata N, Uchikata M, Nakamura S, Matoba R, Tanino M, Matsubara K, Kaneko S. Gene expression profiles in peripheral blood mononuclear cells reflect the pathophysiology of type 2 diabetes2007

    • Author(s)
      Takamura, T., Honda, M., Sakai, Y., Ando, H., Shimizu, A., Ota, T., Sakurai, M., Misu, H., Kurita, S
    • Journal Title

      Biochem Biophys Res Commun 361(2)

      Pages: 379-384

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Increased dyidative stress precodes the onset of high-fat diet-induced insulin resistance and obesity2008

    • Author(s)
      Takamura, T., Nagata, N., Komura, T., Sakai, Y., Honda, M., Kaneko, S
    • Organizer
      Keystone Symposia(X3)
    • Year and Date
      2008-02-22
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] テロメアサイレンシングにおける出芽酵母Ran系遺伝子群の機能2007

    • Author(s)
      林 直之、西本毅治、村上清史、山本健一
    • Organizer
      第30回日本生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      20071211-15
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 足揚タンパク質JSAP1はマウス顆粒前駆細胞の増殖を負に制御する2007

    • Author(s)
      佐藤時春、寅嶋崇、杉原一司、平井宏和、浅野雅秀、善岡克次
    • Organizer
      第30回 日本分子生物大会・第80回日本生化学会大会合同大会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      20071211-15
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 精子形成過程における足場タンパク質JLPの機能解析2007

    • Author(s)
      岩永飛鳥、王光敏、杉原 一司、託見健、檜垣小百合、清水慶子、林基治、浅野雅秀、善岡克次
    • Organizer
      第30回 日本分子生物大会・第80回日本生化学会大会合同大会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      20071211-15
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] La protein is a potent regulator of replication of hepatitis C virus in patients with chronic hepatitis C through internal ribosomal entry site(IRES)directed translation2007

    • Author(s)
      Honda M, Shimazaki T, Murata T, Shimotohno K, lemon S, Kaneko S
    • Organizer
      第56回 米国肝臓学会
    • Place of Presentation
      Boston, USA
    • Year and Date
      20071102-06
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] JNK targets Cdc25B for degradation2007

    • Author(s)
      Yamashita K, Yoshioka K, Matsunaga T, Nakagama H, Ishizaka Y.
    • Organizer
      第66回日本癌学会総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      20071003-05
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 慢性肝炎・肝細胞癌における脂肪化の意義-cDNAマイクロアレイを用いた解析から2007

    • Author(s)
      本多政夫, 上田晃之, 金子周一
    • Organizer
      第91回 日本消化器病学会
    • Place of Presentation
      アクロス福岡
    • Year and Date
      20070613-14
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Different Signaling Pathways in the Liver of Patients with Chronic Hepatitis Induced by Hepatitis B and Hepatitis C Virus Infectionn2007

    • Author(s)
      Honda, M., Yamashita, T., Ueda, T., Takatori, H., Nishino, R., Kaneko, S
    • Organizer
      APASL
    • Place of Presentation
      Kyoto
    • Year and Date
      20070000
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Biological functions of hepatitis B virus X protein2007

    • Author(s)
      Murakami S
    • Organizer
      Japan-Korea Joint Symposium on Recent Advance in Medical Science
    • Place of Presentation
      Chonbok Univ, Korea
    • Year and Date
      2007-11-15
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Comprehensive gene expression analysis of iron metabolism-related genes in patients with chronic viral hepatitis and hepatocellular carcinoma2007

    • Author(s)
      Honda, M., Ueda, T., Yamashita, T., Nishino, R., Takatori, H., Kaneko, S
    • Organizer
      58th American Association of Hepatology
    • Year and Date
      2007-11-06
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] MicroRNA expression profiling combined with analysis of target gene expression in chronic viral hepatitis and hepatocellular carcinoma2007

    • Author(s)
      Ura, S., Honda, M., Ueda, T., Nishino, R., Takatori, H., Nakamura, M., Kaneko, S
    • Organizer
      58th American Association of Hepatology
    • Year and Date
      2007-11-03
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] C型肝炎ウイルス複製制御に関わる宿主因子の検討2007

    • Author(s)
      本多政夫, 島崎猛夫, 金子周一
    • Organizer
      第41回 日本肝臓学会
    • Place of Presentation
      ポートピア横浜
    • Year and Date
      2007-10-06
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] C型肝炎ウイルス複製に関する宿主因子の検討2007

    • Author(s)
      本多政夫, 島崎猛夫, 金子周一
    • Organizer
      第41回 日本肝臓学会
    • Place of Presentation
      ポートピア横浜
    • Year and Date
      2007-10-06
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Functional interaction of hepatitis C virus NS5B with nucleolin GAR domain

    • Author(s)
      Shimakami, T., Kusakawa, T., Honda, M., Kaneko, S., Yohioka, K., Murakami, S
    • Organizer
      15th International symposium on Hepatitis C Virus & Related Viruses
    • Place of Presentation
      Texas
    • Year and Date
      00001005-09
    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2010-02-04  

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