Multi-functions of tankyrase-1 in carcinogenesis

• Project/Area Number: 19370078
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Japanese Foundation For Cancer Research
• Principal Investigator: SEIMIYA Hiroyuki Japanese Foundation For Cancer Research, 癌化学療法センター分子生物治療研究部, 部長 (50280623)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2008: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000); Fiscal Year 2007: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
• Keywords: ポリ(ADP-リボシル)化 / がん / テロメア / 細胞分裂 / 分子標的 / 創薬 / PARP / タンキラーゼ

Research Abstract

タンキラーゼ1は、がん細胞の無限増殖を支持するテロメラーゼの働きを助ける、ポリ(ADP-リボシル)化酵素である。本酵素の本来の働きは良く分かっておらず、特異的阻害剤も得られていない。我々は、タンキラーゼ1の下流で働くTRF1と呼ばれる蛋白質が、がん化の一因となる異常な細胞分裂に寄与することを見出した。また、タンキラーゼ1の働きを遮断する物質を複数同定するとともに、ある種の培養がん細胞に対し、同酵素の阻害が制がん効果を生み出すことを見出した

Research Products

• [Journal Article] Targeting Tankyrase 1 as a therapeutic strategy for BRCA-associated cancer (2009)
  • Author(s): McCabe N, Cerone MA, Ohishi T, Seimiya H, Lord CJ, Ashworth A
  • Journal Title: Oncogene 28 Pages: 1465-1470
• [Journal Article] De novo fatty-acid synthesis and related pathways as molecular targets for cancer therapy (2009)
  • Author(s): Mashima T, Seimiya H, Tsuruo T
  • Journal Title: Br J Caner 100 Pages: 1369-1372
• [Journal Article] Promotion of glioma cell survival by acyl-CoA synthetase 5 under extracellular acidosis conditions (2009)
  • Author(s): Mashima T, Sato S, Sugimoto Y, Tsuruo T, Seimiya H
  • Journal Title: Oncogene 28 Pages: 9-19
• [Journal Article] Telomeres and Telomerase in Cancer, Edited by Hiyama K. 「Tankyrase 1, telomere-binding proteins, and inhibitors」 (2009)
  • Author(s): Seimiya H
  • Journal Title: Humana Press Pages: 281-292
• [Journal Article] De novo fatty-acid synthesis and related pathways as molecular targets for cancer therapy (2009)
  • Author(s): Mashima T
  • Journal Title: British Journal of Cancer 100 Pages: 1369-1372
  • Peer Reviewed
• [Journal Article] Promotion of glioma cell survival by acyl-CoA synthetase 5 under extracellular acidosis conditions (2009)
  • Author(s): Mashima T
  • Journal Title: Oncogene 28 Pages: 9-19
  • Peer Reviewed
• [Journal Article] Telomere elongation by a mutant tankyrase 1 without TRF1 poly(ADP-ribosyl)ation (2008)
  • Author(s): Muramatsu Y, Tahara H, Ono T, Tsuruo T, Seimiya H
  • Journal Title: Exp Cell Res 314 Pages: 1115-1124
• [Journal Article] ATP citrate lyase : activation and therapeutic implications in non-small cell lung cancer (2008)
  • Author(s): Migita T, Narita T, Nomura K, Miyagi E, Inazuka F, Matsuura M, Ushijima M, Mashima T, Seimiya H, Satoh Y, Okumura S, Nakagawa K, Ishikawa Y
  • Journal Title: Cancer Res 68 Pages: 8547-8554
• [Journal Article] Targeting Tankyrase 1 as a therapeutic strategy for BRCA-associated cancer (2008)
  • Author(s): McCabe N
  • Journal Title: Oncogene 28 Pages: 1465-1470
  • Peer Reviewed
• [Journal Article] ATP citrate lyase : activation and therapeutic implications in non-small cell lung cancer (2008)
  • Author(s): Migita T
  • Journal Title: Cancer Research 68 Pages: 8547-8554
  • Peer Reviewed
• [Journal Article] Evaluation of tankyrase inhibition in whole cells (2008)
  • Author(s): Ohishi, T.
  • Journal Title: Methods Mol Biol 405 Pages: 133-146
  • Peer Reviewed
• [Journal Article] Telomere elongation by a mutant tankyrase 1 without TRF1 poly(ADP-ribosyl)ation (2008)
  • Author(s): Muramatsu, Y.
  • Journal Title: Exp Cell Res 314 Pages: 1115-1124
  • Peer Reviewed
• [Journal Article] Cross-species difference in telomeric function of tankyrase 1 (2007)
  • Author(s): Muramatsu Y, Ohishi T, Sakamoto M, Tsuruo T, Seimiya H
  • Journal Title: Cancer Sci 98 Pages: 850-857
• [Journal Article] Evaluation of tankyrase inhibition in whole cells (2007)
  • Author(s): Ohishi T, Tsuruo T, Seimiya H
  • Journal Title: Meth Mol Biol 405 Pages: 133-146
• [Journal Article] hnRNP A3 binds to and protects mammalian telomeric repeats in vitro (2007)
  • Author(s): Tanaka E, Fukuda H, Nakashima K, Tsuchiya N, Seimiya H, Nakagama H
  • Journal Title: Biochem Biophys Res Commun 358 Pages: 608-614
• [Journal Article] hnRNP A3 binds to and protects mammalian telomeric repeats in vitro (2007)
  • Author(s): Tanaka, E.
  • Journal Title: Biochem Biophys Res Commun 358 Pages: 608-614
  • Peer Reviewed
• [Journal Article] Cross-species difference in telomeric function of tankyrase 1 (2007)
  • Author(s): Muramatsu, Y.
  • Journal Title: Cancer Sci 98 Pages: 850-857
  • Peer Reviewed
• [Journal Article] Acyl-CoA synthetase as a cancer survival factor : its inhibition enhances the efficacy of etoposide
  • Author(s): Mashima T, Sato S, Okabe S, Miyata S, Matsuura M, Sugimoto Y, Tsuruo T, Seimiya H
  • Journal Title: Cancer Sci (in press)
  • NAID: 10027193846
• [Journal Article] Acyl-CoA synthetase as a cancer survival factor : its inhibition enhances the efficacy of etoposide
  • Author(s): Mashima T
  • Journal Title: Cancer Science (印刷中)
  • Peer Reviewed
• [Presentation] ポリ(ADP-リボシル)化酵素タンキラーゼ1の自己多量体化によるテロメア機能の調節 (2009)
  • Author(s): 初谷香織、大石智一、杉本芳一、鶴尾隆、清宮啓之
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
  • Year and Date: 2009-03-26
• [Presentation] Telomere fingerprinting and its application to drug sensitivity studies (2009)
  • Author(s): Seimiya H
  • Organizer: The 9th Korea-Japan Symposium on Cancer and Ageing Research
  • Place of Presentation: 韓国Damyang
  • Year and Date: 2009-03-12
• [Presentation] Telomere fingerprinting and its application to drug sensitivity studies (2009)
  • Author(s): 清宮啓之
  • Organizer: The 9th Korea-Japan Symposium on Cancer and Ageing Research
  • Place of Presentation: 韓国・Damyang
  • Year and Date: 2009-03-12
• [Presentation] テロメア・老化関連分子を標的とした新規がん化学療法の開発 (2009)
  • Author(s): 清宮啓之
  • Organizer: 第1回佐賀大学先端研究センター研究推進部門セミナー「がん分子標的療法の新展開」
  • Place of Presentation: 佐賀
  • Year and Date: 2009-02-27
• [Presentation] テロメア動態制御ネットワークの解明と薬剤反応性研究への応用 (2009)
  • Author(s): 清宮啓之
  • Organizer: 岩手医科大学・化学療法基盤情報支援班共催シンポジウム「 抗がん剤創薬の新たな展開」
  • Place of Presentation: 岩手
  • Year and Date: 2009-01-16
• [Presentation] テロメア動態制御ネットワークの解明と薬剤反応性研究への応用 (2009)
  • Author(s): 清宮啓之
  • Organizer: 岩手医科大学・化学療法基盤情報支援班共催シンポジウム「抗がん剤創薬の新たな展開」
  • Place of Presentation: 岩手
  • Year and Date: 2009-01-16
• [Presentation] テロメア伸長がもたらすがん細胞の遺伝子発現変化 (2008)
  • Author(s): 平島匡太郎、鶴尾隆、清宮啓之
  • Organizer: 第31回日本分子生物学会年会第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] テロメア伸長がもたらすがん細胞の遺伝子発現変化 (2008)
  • Author(s): 平島匡太郎
  • Organizer: 第31回日本分子生物学会年会(第81回日本生化学会大会合同大会)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] TRF1 mediates mitotic abnormalities induced by Aurora A overexpression (2008)
  • Author(s): 大石智一、鶴尾隆、清宮啓之
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2008-10-29
• [Presentation] Construction of the Telomere Fingerprint Database, a novel platform for telomere dynamics and drug sensitivity studies (2008)
  • Author(s): 清宮啓之、村松由起子、田原栄俊、上野勝、矢守隆夫、鶴尾隆
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2008-10-28
• [Presentation] Tankyrase 1 suppresses oncogene-induced mitotic abnormalities (2008)
  • Author(s): Seimiya H, Ohishi T, Tsuruo T
  • Organizer: 欧州EMBOカンファレンス「Telomeres and the DNA Damage Response」
  • Place of Presentation: スイスVillars-sur-Ollon
  • Year and Date: 2008-09-18
• [Presentation] Tankyrase 1 suppresses oncogene-induced mitotic abnormalities (2008)
  • Author(s): 清宮啓之
  • Organizer: 欧州EMBOカンファレンス「Telomeres and the DNA Damage Response」
  • Place of Presentation: スイス・Villars-sur-Ollon
  • Year and Date: 2008-09-18
• [Presentation] 細胞分裂におけるテロメア結合蛋白質の新たな機能 (2008)
  • Author(s): 清宮啓之
  • Organizer: 第26回日本ヒト細胞学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2008-08-30
• [Presentation] 内分泌療法抵抗性前立腺がんにおけるアンドログン受容体シグナル評価系の構築 (2008)
  • Author(s): 馬島 哲夫
  • Organizer: 第8回関東ホルモンと癌研究会
  • Place of Presentation: 東京
  • Year and Date: 2008-01-19
• [Presentation] ヒトDNA複製因子(RPA)のテロメアにおける機能解析 (2007)
  • Author(s): 小林 由佳
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] Anticancer effect of a telomerase inhibitor, MST-312, associated with telomere length and a premature aging-related protein (2007)
  • Author(s): Seimiya H, Muramatsu Y, Sato S, Tahara H, Yamori T, Tsuruo T
  • Organizer: AACR Special Conference "The Role of Telomeres and Telomerase in Cancer Research"
  • Place of Presentation: San Francisco, CA, USA
  • Year and Date: 2007-12-07
• [Presentation] Anticancer effect of a telomerase inhibitor,MST-312,associated with telomere length and a premature aging related protein (2007)
  • Author(s): Seimiya, H.
  • Organizer: AACR Special Conference "The Role of Telomeres and Telomerase in Cancer Research"
  • Place of Presentation: San Francisco CA,USA
  • Year and Date: 2007-12-07
• [Presentation] Tankyrase 1 suppresses mitotic abnormalities induced by Aurora A overexpression (2007)
  • Author(s): 大石智一、鶴尾隆、清宮啓之
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] Cross-species difference in telomeric function of tankyrase 1 (2007)
  • Author(s): 村松由起子、大石智一、鶴尾隆、清宮啓之
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] Involvement of Acyl-CoA synthetase 5 in survival of human glioma cells (2007)
  • Author(s): 馬島 哲夫
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] Cancer therapy by a telomerase inhibitor, MST-312 (2007)
  • Author(s): Seimiya H, Tsuruo T
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] Intracellular reactions induced by a telomerase inhibitor and their impact on human cancer cell growth (2007)
  • Author(s): Seimiya H, Tsuruo T
  • Organizer: The 8th Japan-Korea Joint Symposium on Cancer and Ageing Research
  • Place of Presentation: 岐阜
  • Year and Date: 2007-08-11
• [Presentation] Tankyrase 1 suppresses mitotic abnormalities induced by Aurora A overexpression (2007)
  • Author(s): Ohishi T, Tsuruo T, Seimiya H
  • Organizer: The 8th Japan-Korea Joint Symposium on Cancer and Ageing Research
  • Place of Presentation: 岐阜
  • Year and Date: 2007-08-11
• [Presentation] グリオーマ生存における脂肪酸代謝酵素アシルCoAシンターゼの関与とその分子機構 (2007)
  • Author(s): 馬島 哲夫
  • Organizer: 第11回がん分子標的治療研究会総会
  • Place of Presentation: 大阪
  • Year and Date: 2007-07-06
• [Presentation] タンキラーゼ1の細胞分裂における機能的関与 (2007)
  • Author(s): 大石智一、鶴尾隆、清宮啓之
  • Organizer: 第11回がん分子標的治療研究会総会
  • Place of Presentation: 大阪
  • Year and Date: 2007-07-05
• [Presentation] Acute anti-proliferative effect of a synthetic telomerase inhibitor, MST-312, on human cancer cells (2007)
  • Author(s): Seimiya H, Muramatsu Y, Sato S, Sakamoto M, Ohishi T, Tahara H, Yamori T, Tsuruo T
  • Organizer: Cold Spring Harbor Laboratory Meeting on Telomeres & telomerase
  • Place of Presentation: Cold Spring Harbor, NY, USA
  • Year and Date: 2007-05-04
• [Presentation] Acute anti-proliferative effect of a synthetic telomerase inhibitor,MST-312,on human cancer cells (2007)
  • Author(s): Seimiya, H.
  • Organizer: Cold Spring Harbor Laboratory Meeting on Telomeres&telomerase
  • Place of Presentation: Cold Siring Harbor NY,USA
  • Year and Date: 2007-05-04
• [Book] Telomeres and Telomerase in Cancer(Tankyrase 1, telomere-binding proteins, and inhibitors)(edited by Hiyama K) (2009)
  • Author(s): Seimiya H, Tsuruo T
  • Publisher: Humana Press
• [Remarks] 和文
  • URL: http://www.jfcr.or.jp/laboratory/ccc/molecularbiotherapy/index.html
• [Remarks] 英文
  • URL: http://www.jfcr.or.jp/laboratory/english/ccc/molecularbiotherapy/index.html
• [Remarks]
  • URL: http://www.jfcr.or.jp/laboratory/ccc/molecularbiotherapy/index.html
• [Remarks]
  • URL: http://www.jfcr.or.jp/laboratory/ccc/molecularbiotherapy/index.html