Analysis of the physiological function of the KSHV encoded kinases

• Project/Area Number: 19590097
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: University of Yamanashi (2008); Hokkaido University (2007)
• Principal Investigator: FUJIMURO Masahiro University of Yamanashi, 大学院・医学工学総合研究部, 准教授 (20360927)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: ウイルス / 感染症 / ゲノム創薬 / 創薬 / がん

Research Abstract

カポジ肉腫関連ヘルペスウイルス(KSHV)ゲノムがコードするウイルス性リン酸化酵素の基質特異性や生理機能の解析は、KSHVの病原性の解明と抗KSHV薬の分子設計に必要不可欠な研究課題である。そこで、我々は、KSHVの発現するチミジンリン酸化酵素(ORF21)やリン酸基転移酵素(ORF36)の機能解析を行なった。その結果、KSHVのORF21は、抗ヘルペスウイルス薬ACVや他のプリン・ヌクレオシド誘導体へのリン酸化効率は非常に低いことが明らかになった。一方で、ORF36の機能解析により、ORF36は複数の細胞性因子とKSHVのウイルス蛋白質をリン酸化し、NF-κB等の細胞内シグナル伝達の制御も行なっていることが明らかとなった。

Research Products

• [Journal Article] Epstein-Barr virus-derived EBNA2 regulates STAT3 activation (2009)
  • Author(s): Muromoto R, Ikeda O, Okabe K, Togi S, Kamitani S, Fujimuro M, Harada S, Oritani K, Matsuda T.
  • Journal Title: Biochem. Biophys. Res. Commun 378 Pages: 439-443
  • NAID: 120001024527
  • Peer Reviewed
• [Journal Article] ウイルスによる分子海賊 : カポジ肉腫関連ヘルペスウイルスによるユビキチン経路とシグナル伝達の脱制御 (2009)
  • Author(s): 藤室雅弘
  • Journal Title: 山梨医科学雑誌 印刷中
• [Journal Article] BS69 negatively regulates the canonical NF-kB activation induced by Epstein-Barr virus-derived LMP1 (2009)
  • Author(s): Ikeda, O, Sekine Y, Mizushima A, Oritani K, Yasui T, Fujimuro M, Muromoto R, Nanbo A, and Matsuda T
  • Journal Title: FEBS Lett (In press)
  • Peer Reviewed
• [Journal Article] An unusual case of chronic relapsing tetanus associated with mandibular osteomyelitis (2009)
  • Author(s): Wakasaya Y, Watanabe M, Tomiyama M, Suzuki C, Jackson M, Fujimuro M, Kimura T, Seino Y, Kawarabayashi T, Yamamoto-Watanabe Y, Matsubara E, Shirahama I, Takamura A, Nakahata N, Shoji M
  • Journal Title: Intern Med (in press)
  • NAID: 130000121961
  • Peer Reviewed
• [Journal Article] SMRT regulates enhanced activation of STAT3 by Epstein-Barr virus-derived EBNA2 (2009)
  • Author(s): Ikeda, O, Togi S, Kamitani S, Muromoto R, Sekine Y, Nanbo A, Fujimuro M, and Matsuda T
  • Journal Title: Biol. Pharm. Bull (in press)
  • Peer Reviewed
• [Journal Article] Epstein- Barr virus-derived EBNA2 regulates STAT3 activation. (2009)
  • Author(s): Muromoto R., et al
  • Journal Title: Biochem. Biophys. Res. Commun. 378 Pages: 439-443
  • Peer Reviewed
• [Journal Article] Nuclear DISC1 regulates CRE-mediated gene transcription and sleep homeostasis in the fruit fly (2008)
  • Author(s): Sawamura N, Ando T, Maruyama Y, Fujimuro M, Mochizuki H, Honjo K, Shimoda M, Toda H, Sawamura-Yamamoto T, Makuch LA, Hayashi A, Ishizuka K, Cascella NG, Kamiya A, Ishida N, Tomoda T, Hai T, Furukubo-Tokunaga K, Sawa A
  • Journal Title: Mol Psychiatry 13 Pages: 1138-1148
  • Peer Reviewed
• [Journal Article] Nuclear DISCI regulates CRE-mediated gene transcription and sleep homeostasis in the fruit fly. (2008)
  • Author(s): Sawamura N., et al
  • Journal Title: Mol. Psychiatry 13 Pages: 1138-1148
  • Peer Reviewed
• [Journal Article] 9-(2-C-Cyano-2-deoxy-beta-d-arabinopentofuranosyl) guanine, a Potential Antitumor Agent against B-Lymphoma Infected with Kaposi's Sarcoma-Associated Herpesvirus (2007)
  • Author(s): Ohtawa M, Ichikawa S, Teishikata Y, Fujimuro M, Yokosawa H, Matsuda A.
  • Journal Title: J. Med. Chem. 50 Pages: 2007-2010
  • Peer Reviewed
• [Journal Article] Transient activation of transgene expression by hydrodynamics-based injection may cause rapid decrease in plasmid DNA expression (2007)
  • Author(s): Ochiai H, Fujimuro H, Yokosawa H, Harashima H, Kamiya H.
  • Journal Title: Gene Therapy 14 Pages: 1152-1159
  • NAID: 120000947243
  • Peer Reviewed
• [Journal Article] Molecular Piracy : Manipulation of the Ubiquitin System by Kaposi's Sarcoma-Associated Herpesvirus (2007)
  • Author(s): Fujimuro M, Hayward SD, Yokosawa H.
  • Journal Title: Rev. Med. Virol.17 Pages: 405-422
  • Peer Reviewed
• [Journal Article] 9-(2-C-Cyano-2-deoxy-beta-d-arabino-pentofuranosyl)guanine, a Potential Antitumor Agent against B-Lymphoma Infected with Kaposi's Sarcoma-Associated Herpesvirus. (2007)
  • Author(s): Ohtawa M., et. al.
  • Journal Title: J. Med Chem. 50 Pages: 2007-2010
  • Peer Reviewed
• [Journal Article] Transient activation of transgene expression by hydrodynamics-based injection may cause rapid decrease in plasmid DNA expression. (2007)
  • Author(s): Ohtawa M., et. al.
  • Journal Title: Gene Therapy 14 Pages: 1152-1159
  • Peer Reviewed
• [Journal Article] Molecular Piracy: Manipulation of the Ubiquitin System by Kaposi's Sarcoma-Associated Herpesvirus. (2007)
  • Author(s): Fujimuro M., et. al.
  • Journal Title: Reviews in Medical Virology 17 Pages: 405-422
  • Peer Reviewed
• [Presentation] カポジ肉腫関連ヘルペスウイルスによる細胞内蛋白質分解系の脱制御 (2009)
  • Author(s): 藤室雅弘、手石方康宏、平敬宏、横沢英良
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都国際会議場
• [Presentation] A viral mechanism for dysregulation of post-translational modification in Kaposi's sarcoma-associated herpesvirus latency (2008)
  • Author(s): Masahiro Fujimuro and Hideyoshi Yokosawa
  • Organizer: 17^<th> Meeting of Methods in Protein Structure Analysis
  • Place of Presentation: Sapporo
• [Presentation] A viral mechanism for dysregulation of post-translational modificat ion in Kaposi's sarcoma-associated herpesvirus latency. (2008)
  • Author(s): Masahiro Fujimuro, Hideyoshi Yokosawa
  • Organizer: 17th Meeting of Methods in Protein Structure Analysis (MPSA2008)
  • Place of Presentation: 札幌
• [Presentation] KSHV感染特異的抗がん薬CNDAGの開発 (2007)
  • Author(s): 山田浩二、藤室雅弘、横沢英良、松田彰
  • Organizer: 第55回日本ウイルス学会年会一般口演
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2007-10-23
• [Presentation] カポジ肉腫関連ヘルペスウイルスによる脱ユビキチン化酵素の制御機構 (2007)
  • Author(s): 藤室雅弘、横沢英良
  • Organizer: 第55回日本ウイルス学会年会ワークショップ
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2007-10-23
• [Presentation] カポジ肉腫関連ヘルペスウイルスによる脱ユビキチン化酵素の制御機構 (2007)
  • Author(s): 藤室雅弘
  • Organizer: 第55回日本ウイルス研究会 ワークショップ
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2007-10-23
• [Presentation] カポジ肉腫関連ヘルペスウイルスの発がん機構 (2007)
  • Author(s): 藤室雅弘
  • Organizer: 第31回阿蘇シンポジュウム招待講演
  • Place of Presentation: 阿蘇リゾートヴィリオホテル
  • Year and Date: 2007-07-27
• [Presentation] KSHV感染特異的抗がん薬CNDAGの開発 (2007)
  • Author(s): 山田浩二、藤室雅弘、手石方康弘、横沢英良、大多和正樹、市川聡、松田彰
  • Organizer: 第4回EBウイルス研究会一般口演
  • Place of Presentation: 東京大学医学部
  • Year and Date: 2007-06-29
• [Book] プロテアソームと蛋白質分解
  • Author(s): 藤室雅弘、横沢英良
  • Publisher: 生物薬科学実験講座(印刷中)