Analysis of ovarian carcinogenesis due to monoubiquitylation of gankyrin that is one of proteasome-interacting -proteins (PIPs)

• Project/Area Number: 19591931
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Kyoto University
• Principal Investigator: HIGASHITSUJI Hisako Kyoto University, 医学研究科, 助教 (20402852)
• 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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: プロテアソーム / ガンキリン / モノユビキチン / 卵巣癌 / モノユビキチン化 / PIP / 卵巣がん / nedd8 / ISG15 / MDM2 / がん抑制遺伝子

Research Abstract

癌遺伝子産物であるガンキリンのモノULM(ubiquitin-like-modifiers)(ユビキチン、nedd8、sumo1-4、ISG15、urm1など)化、特にnedd8化という翻訳後修飾はガンキリンによる細胞癌化の働きを変化させた。卵巣がん細胞において、モノnedd8化ガンキリンは癌抑制遺伝子産物であるp53よりpRBのほうにMDM2の基質特異性を変化させ、pRBをより分解する傾向を示した。Nedd8系の成分は抗がん剤のターゲットとなりうることが示唆された。

Research Products

• [Journal Article] Association of gankyrin protein expression with early clinical stages and IGFBP-5 expression in human hepatocellular carcinoma (2008)
  • Author(s): Umemura A, Itoh Y, Itoh K, Yamaguchi K, Nakajima T, Higashitsuji H, Onoue H, Fukumoto M, Okanoue T, Fujita J
  • Journal Title: Hepatology 47(2) Pages: 493-502
  • Peer Reviewed
• [Journal Article] A novel protein overexpressed in hepatoma accelerates export of NF-kappaB from the nucleus and inhibits p53-dependent apoptosis (2008)
  • Author(s): Higashitsuji H, Higashitsuji H, Nagao T, Nonoguchi K, Fujii S, Itoh K, Fujita J
  • Journal Title: Cancer Cell 2(4) Pages: 335-346
  • Peer Reviewed
• [Journal Article] Association of gankyrin protein expression with early clinical stages and insulin-like growth factor-binding protein 5 expression in human hepatocellular carcinoma. (2008)
  • Author(s): Umemura, A., Itoh. Y., Itoh, K., Yamaguchi, K., Nakajima. T., Higashitsuji, H., Onoue, H., Fukumoto, M., Okanoue, T., Fujita, J.
  • Journal Title: Hepatology 47 Pages: 493-502
  • Peer Reviewed
• [Journal Article] The oncoprotein gankyrin interacts with RelA and suppresses NF kappaB activity (2007)
  • Author(s): Higashitsuji H, Higashitsuji H, Liu Y, Masuda T, Fujita T, Abdel-Aziz HI, Kongkham S, Dawson S, John Mayer R, Itoh Y, Sakurai T, Itoh K, Fujita J
  • Journal Title: Biochem Biophys Res Commun 363(3) Pages: 879-84
  • Peer Reviewed
• [Journal Article] Enhanced deacetylation of p53 by the anti-apoptotic protein HSCO1 in association with histone deacetylase 1 (2007)
  • Author(s): Higashitsuji H, Higashitsuji H, Masuda T, Liu Y, Itoh K, Fujita J
  • Journal Title: J Biol Chem 282(18) Pages: 13716-25
  • Peer Reviewed
• [Journal Article] The oncoprotein gankyrin interacts with RelA and suppresses NFkappaB activity. (2007)
  • Author(s): Hiroaki Higashitsuji, et. al.
  • Journal Title: Biochem Biophys Res Commun 363 Pages: 879-884
  • Peer Reviewed
• [Journal Article] Enhanced deacetylation of p53 by the anti-apoptotic protein HSCO in association with histone deacetylase 1. (2007)
  • Author(s): Hisako Higashitsuji, et. al.
  • Journal Title: J Biol Chem 282 Pages: 13716-25
  • Peer Reviewed
• [Journal Article] The oncoprotein gankyrin binds to MDM2/HDM2, enhancing ubiquitylation and degradation of p53 (2005)
  • Author(s): Higashitsuji H, Higashitsuji H, Itoh K,Sakurai T, Nagao T, Sumitomo Y, Masuda T, Dawson S, Shimada Y, Mayer RJ, Fujita J
  • Journal Title: Cancer Cell 8(1) Pages: 75-87
  • Peer Reviewed
• [Journal Article] Management of ovarian hyperstimulation due to follicle -stimulating hormone-secreting gonadotroph adenoma (2004)
  • Author(s): Murakami T, Higashitsuji H, Yoshinaga K, Terada Y, Ito K, Ikeda H
  • Journal Title: BJOG 111(11) Pages: 1297-1300
  • Peer Reviewed
• [Presentation] 卵巣癌で過剰発現する癌遺伝子産物ガンキリンはNFkappaB(RelA)と結合しその転写活性化能を抑制する (2009)
  • Author(s): 東辻久子
  • Organizer: 第61回日本産科婦人科学会学術講演会
  • Place of Presentation: 国立京都国際会館、京都市
  • Year and Date: 2009-04-05
• [Presentation] 卵巣癌で過剰発現する癌遺伝子産物ガンキリンは NFkappaB(RelA)と結合しその転写活性化能を抑制する。 (2009)
  • Author(s): 東辻久子
  • Organizer: 第61回日本産科婦人科学会学術講演会
  • Place of Presentation: 国立京都国際会館、京都市
  • Year and Date: 2009-04-05
• [Presentation] 卵巣癌で過剰発現する抗アポトーシス蛋白HSCOは、脱アセチル化酵素HDAC1をp53にリクルートすることにより、化学療法剤耐性を賦与する (2007)
  • Author(s): 東辻久子
  • Organizer: 第59回日本産科婦人科学会学術講演会
  • Place of Presentation: 国立京都国際会館、京都市
  • Year and Date: 2007-04-16
• [Presentation] 卵巣癌で過剰発現する抗アポトーシス蛋白HSCOは、脱アセチル化酵素HDAC1をp53にリクルートすることにより、化学療法剤耐性を賦与する (2007)
  • Author(s): 東辻久子
  • Organizer: 第59回日本産科婦人科学会学術講演会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2007-04-16