Rae1-Nup98の準安定状態複合体間の相互作用解析に関する探索

• Project Area: Integrative understanding of biological processes mediated by transient macromolecular complexes; New technology for visualizing physiologically metastable states.
• Project/Area Number: 22121506
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Complex systems
• Research Institution: Kanazawa University
• Principal Investigator: WONG WR (WONG W・R) 金沢大学, フロンティアサイエンス機構, 特任准教授 (30464035)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000); Fiscal Year 2011: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2010: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
• Keywords: 核膜孔複合体 / Rae1 / Nup98 / 有糸分裂期 / NuMA / 紡錘体 / 物質輸送 / 異数化 / NPC / 染色体不安定性

Research Abstract

核膜孔複合体(NPC)は、核-細胞質間でのタンパク質、RNA等の選択的物質輸送を制御している(橋爪ら 生化学 2011)。30種類以上あるNPCタンパク質の一つRae1(RNA export factorl)は、Nup98と共にRNAを輸送することが知られている。最近の研究ではいくつかのヌクレオポリンの中には紡錘体形成、及び、有糸分裂後期開始に影響を与え、細胞の癌化に関与するものがあることが明らかになってきた(Funasaka and Wong, Cancer Metasta Rev 2011; Nakano et al., Cell Cycle 2011)。一方、研究代表者は最近、Rae1がNuMA及びSMC1と相互作用することを見出し、この相互作用の変化が多くの癌で見いだされる染色体の異数化・多極紡錘体を引き起こすことを発見した。そこで本研究課題では、Rae1-Nup98の細胞質-核間輸送、及び有糸分裂期中の詳細な機能を分子細胞生物学、及び、構造生物学の両側面から理解することを目的とした。
当該年度は、急性骨髄性白血病(AML)細胞中の染色体転座に多くみられるキメラタンパク質Nup98/HoxA9を解析した。通常Nup98は、間期では核膜孔に、有糸分裂期では紡錘体に局在するが、キメラタンパク質Nup98/HoxA9は、間期では核内に、有糸分裂期では染色体上に局在が変化していた。これらのデータをまとめ論文を発表した(Funasaka et. al., Cell Cycle 2011)。また、核膜孔複合体の構造と機能についての総説を生化学に(橋爪ら 生化学 2011)、ヌクレオポリンの一つNup88についての総説を生体の科学にて発表した(橋爪ら 生体の科学2011)。さらに、AKTAタンパク質精製装置を用いて高純度のRae1タンパク質を精製することに成功することができた。

Research Products

• [Journal Article] RNA export factor RAE1 contributes to NUP98-HOXA9-mediated leukemogenesis (2011)
  • Author(s): Funasaka T, Nakano H, Wu Y, Hashizume C, Gu L, Nakamura T, Wang W, Zhou P, Moore M, Sato H, Wong RW
  • Journal Title: Cell Cycle Volume: 10 Issue: 9 Pages: 1456-1467
  • DOI: 10.4161/cc.10.9.15494
  • Peer Reviewed
• [Journal Article] The role of nuclear pore complex in tumor microenvironment and metastasis (2011)
  • Author(s): Funasaka T, Wong RW
  • Journal Title: Cancer Metasta Rev Volume: 30 Issue: 2 Pages: 239-251
  • DOI: 10.1007/s10555-011-9287-y
  • Peer Reviewed
• [Journal Article] Unexpected role of nucleoporins in coordination of cell cycle progression (2011)
  • Author(s): Nakano H, Wang W, Hashizume C, Funasaka T, Sato H, Wong R
  • Journal Title: Cell Cycle Volume: 10 Issue: 3 Pages: 425-433
  • DOI: 10.4161/cc.10.3.14721
  • Peer Reviewed
• [Journal Article] 核膜孔複合体タンパク質Nup88 (2011)
  • Author(s): 橋爪智恵子, Wong RW
  • Journal Title: 生体の科学 Volume: 62 Pages: 392-393
• [Journal Article] 核膜孔複合体の構造と機能 (2011)
  • Author(s): 橋爪智恵子, Wong RW
  • Journal Title: 生化学 Volume: 83 Pages: 957-965
• [Journal Article] The role of nuclear pore complex in tumor microenvironment and metastasis. (2011)
  • Author(s): Funasaka T, Wong RW
  • Journal Title: Cancer Metastasis Rev Volume: 30 Pages: 239-251
  • Peer Reviewed
• [Journal Article] RNA Export factor RAE1 contributes to NUP98-HOXA9-mediated leukemogenesis. (2011)
  • Author(s): Funasaka T, Nakano H, Wu Y, Hashizume C, Gu L, Nakamura T, Wang W, Zhou P, Moore M, Sato H, Wong RW
  • Journal Title: Cell Cycle Volume: (accepted)
  • Peer Reviewed
• [Journal Article] GI24 enhances tumor invasiveness by regulating cell surface membrane-type 1 matrix metalloproteinase. (2010)
  • Author(s): Sakr MA, Takino T, Domoto T, Nakano H, Wong RW, Sasaki M, Nakamura Y, Sato H
  • Journal Title: Cancer Science Volume: 101 Pages: 2368-2374
  • Peer Reviewed
• [Journal Article] Unexpected role of nucleoporins in coordination of cell cycle progression. (2010)
  • Author(s): Nakano H, Wang W, Hashizume C, Funasaka T, Sato H, Wong RW
  • Journal Title: Cell Cycle Volume: 10 Pages: 425-433
  • Peer Reviewed
• [Presentation] 白血病発症過程における核膜孔複合体因子の役割 (2012)
  • Author(s): 船坂龍善、小林亜紀子、橋爪智恵子、中村卓郎、佐藤博、Wong RW
  • Organizer: 第117回日本解剖学会総会・全国学術集会
  • Place of Presentation: 山梨県(山梨大学)
  • Year and Date: 2012-03-26
• [Presentation] NUP98-HOXA9による白血病発症機構におけるヌクレオポリンRAE1の役割 (2011)
  • Author(s): 船坂龍善、中野博、橋爪智恵子、中村卓郎、佐藤博、Wong RW
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 神奈川県(パシフィコ横浜)
  • Year and Date: 2011-12-16
• [Presentation] The role of nucleoporins in coordination of cell cycle progression and tumorigenesis (2011)
  • Author(s): Wong RW
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 神奈川県(パシフィコ横浜)
  • Year and Date: 2011-12-15
• [Presentation] The role of mRNA export factor RAE1 in leukemogenesis (2011)
  • Author(s): Funasaka T, Hashizume C, Kobayashi A, Nakamura T, Wong RW
  • Organizer: The 51th Annual Meeting of the American society of cell biology
  • Place of Presentation: Denver, Colorado, USA. (Denver Conventional Center)
  • Year and Date: 2011-12-04
• [Presentation] 核膜孔複合体因子による白血病発症機構に関する研究 (2011)
  • Author(s): 船坂龍善、小林亜紀子、橋爪智恵子、Wong RW
  • Organizer: 第71回日本解剖学会中部支部学術集会
  • Place of Presentation: 愛知県(名古屋大学)
  • Year and Date: 2011-10-15
• [Presentation] 核膜孔複合体因子による新規癌治療法の可能性の検討 (2011)
  • Author(s): Wong RW
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 愛知県(名古屋国際会議場)
  • Year and Date: 2011-10-05
• [Presentation] Nucleoporin Rael contributes to leukemogenic activity of Nup98-HoxA9 (2011)
  • Author(s): 船坂龍善、中野博、橋爪智恵子、Wang W、中村卓郎、佐藤博、Wong RW
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 愛知県(名古屋国際会議場)
  • Year and Date: 2011-10-05
• [Presentation] Nucleoporin function and cancinogenesis (2011)
  • Author(s): Wong RW
  • Organizer: West China hospital, Sichuan University
  • Place of Presentation: Sichuan, China (Sichuan University)
  • Year and Date: 2011-09-28
• [Presentation] Dynamic topologies and functions for nucleoporins in the coordination of cell cycle progression (2011)
  • Author(s): 船坂龍善、小林亜紀子、Xiao S、Wang W、橋爪智恵子、Wong RW
  • Organizer: 第11回日本蛋白質科学会年会
  • Place of Presentation: 大阪(ホテル阪急エキスポパーク)
  • Year and Date: 2011-06-08
• [Presentation] Nucleoporin mitotic functions and carcinogenesis (2011)
  • Author(s): Wong RW
  • Organizer: International Symposium on Tumor Biology in Kanazawa-The 11th Spring Symposium of the Molecular Biology Society of Japan
  • Place of Presentation: 石川県(石川県立音楽堂)(招待講演)
  • Year and Date: 2011-05-25
• [Presentation] The role of Rael in NUP98HOXA9 leukemogenesis (2011)
  • Author(s): 船坂龍善、中野博、橋爪智恵子、Wang W、佐藤博、Wong RW
  • Organizer: 日本分子生物学会第11回春季シンポジウム
  • Place of Presentation: 石川県(石川県立音楽堂)
  • Year and Date: 2011-05-25
• [Presentation] Characterization of the role of the tumor marker Nup88 in mitosis (2011)
  • Author(s): 橋爪智恵子、Wang W、Xiao S、Wong RW
  • Organizer: 日本分子生物学会第11回春季シンポジウム
  • Place of Presentation: 石川県(石川県立音楽堂)
  • Year and Date: 2011-05-25
• [Presentation] RNA export factor Rael interacts with cohesin subunit SMC1 at the mitotic spindle pole (2011)
  • Author(s): Wang W、橋爪智恵子、佐藤博、Wong RW
  • Organizer: 日本分子生物学会第11回春季シンポジウム
  • Place of Presentation: 石川県(石川県立音楽堂)
  • Year and Date: 2011-05-25
• [Presentation] C Nucleoporin Tpr associates with dynein compleX preventing aneuploidy formation in cancer cells (2011)
  • Author(s): 小林亜紀子、船坂龍善、Wang W、Wong RW
  • Organizer: 日本分子生物学会第11回春季シンポジウム
  • Place of Presentation: 石川県(石川県立音楽堂)
  • Year and Date: 2011-05-25
• [Presentation] Nucleoporinの準安定状態複合体間の相互作用解析に関する探索 (2011)
  • Author(s): Wong RW
  • Organizer: 新学術領域研究「過渡的複合体」班会議
  • Place of Presentation: 山梨県(リゾナーレ小淵沢)
  • Year and Date: 2011-05-17
• [Presentation] Nucleoporin Nup88 orchestrates proper chromosomal segregation through its interaction with Cdc20 during mitosis (2011)
  • Author(s): Hashizume C, Wong RW
  • Organizer: The Annual Meeting of the American Society for Biochemistry and Molecular Biology
  • Place of Presentation: Washington, D.C., USA (Washington Conventional Center)
  • Year and Date: 2011-04-10
• [Presentation] RNA export factor Rael interacts with cohesin subunit SMC1 at the mitotic spindle pole (2011)
  • Author(s): Funasaka T, Wong RW
  • Organizer: The Annual Meeting of the American Society for Biochemistry and Molecular Biology
  • Place of Presentation: Washington, D.C., USA (Washington Conventional Center)
  • Year and Date: 2011-04-10
• [Presentation] Nucleoporin Tpr interacts with dynein preventing chromosome lagging Formation (2011)
  • Author(s): Nakano H, Funasaka T, Hashizume C, Wang W, Wong RW
  • Organizer: The Annual Meeting of the American Society for Biochemistry and Molecular Biology
  • Place of Presentation: Washington, D.C., USA (Washington Conventional Center)
  • Year and Date: 2011-04-10
• [Presentation] A critical role of translocated promoter region (Tpr) in chromosome segregation and cell division in cancer (2011)
  • Author(s): Funasaka T, Nakano H, Wong RW
  • Organizer: The 102nd Annual Meeting of the American Association for Cancer Research
  • Place of Presentation: Orland, FL, USA (Orland Conventional Center)
  • Year and Date: 2011-04-05
• [Presentation] Nucleoporin function and carcinogenesis. (2011)
  • Author(s): Wong RW
  • Organizer: Peking University School of life Science
  • Place of Presentation: Beijing, China (Peking University)
  • Year and Date: 2011-02-18
• [Presentation] Nucleoporin function and tumorigenesis. (2011)
  • Author(s): Wong RW
  • Organizer: Cancer Hospital, Breast Cancer Institute, Fudan University
  • Place of Presentation: Shanghai, China (Fudan University)
  • Year and Date: 2011-02-17
• [Presentation] Nucleoporin function and tumorigenesis. (2011)
  • Author(s): Wong RW
  • Organizer: 金沢大学がん研究所Oncologyセミナー
  • Place of Presentation: 石川県(金沢大学がん研究所)
  • Year and Date: 2011-01-26
• [Presentation] Nucleoporin translocated promoter region (Tpr) associates with dynein complex is essential for accurate chromosome segregation. (2010)
  • Author(s): Funasaka T, Nakano H, Wong RW
  • Organizer: The 50th Annual Meeting of the American society of cell biology.
  • Place of Presentation: Philadelphia, USA (Philadelphia convention center)
  • Year and Date: 2010-12-13
• [Presentation] Nucleoporin Nup88 associates with Cdc20 during mitosis. (2010)
  • Author(s): Hashizume C, Wong RW
  • Organizer: The 50th Annual Meeting of the American society of cell biology.
  • Place of Presentation: Philadelphia, USA (Philadelphia convention center)
  • Year and Date: 2010-12-12
• [Presentation] 核膜孔タンパク質Nup88の有糸分裂期における役割の解析 (2010)
  • Author(s): 橋爪智恵子、Wong RW
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 兵庫県(神戸ポートアイランド)
  • Year and Date: 2010-12-09
• [Presentation] Nucleoporin Translocated Promoter Region (Tpr) associates with Dyne in complex, preventing chromosome lagging formation during mitosis. (2010)
  • Author(s): 中野博、船坂龍善、橋爪智恵子、Wong RW
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 兵庫県(神戸ポートアイランド)
  • Year and Date: 2010-12-09
• [Presentation] Nucleoporin functionand cancer pathogenesis. (2010)
  • Author(s): Wong RW
  • Organizer: 17^<th> Hong Kong International Cancer Congress
  • Place of Presentation: Hong Kong, China (Cheung Kung Hai Conference Centre)
  • Year and Date: 2010-11-03
• [Presentation] Nucleoporin Tpr associates with dynein complex preventing chromosome lagging formation. (2010)
  • Author(s): Nakano H, Funasaka T, Hashizume C, Wang W, Wong RW
  • Organizer: 17^<th> Hong Kong International Cancer Congress
  • Place of Presentation: Hong Kong, China (Cheung Kung Hai Conference Centre)
  • Year and Date: 2010-11-03
• [Presentation] ヌクレオポリンTprの有糸分裂期における役割 (2010)
  • Author(s): 船坂龍善、中野博、橋爪智恵子、Wong RW
  • Organizer: 第19回日本がん転移学会学術集会・総会
  • Place of Presentation: 石川県(金沢市文化ホール)
  • Year and Date: 2010-06-16
• [Presentation] 腫瘍マーカーNup98の細胞分裂中における役割 (2010)
  • Author(s): 橋爪智恵子、中野博、Wong RW
  • Organizer: 第19回日本がん転移学会学術集会・総会
  • Place of Presentation: 石川県(金沢市文化ホール)
  • Year and Date: 2010-06-16
• [Presentation] Nup88トランスジェニックマウスの表現型解析 (2010)
  • Author(s): 中野博、佐藤博、Wong RW
  • Organizer: 第19回日本がん転移学会学術集会・総会
  • Place of Presentation: 石川県(金沢市文化ホール)
  • Year and Date: 2010-06-16
• [Presentation] Rae1-Nup98の準安定状態複合体間の相互作用解析に関する探索 (2010)
  • Author(s): Wong RW
  • Organizer: 新学術領域研究「過渡的複合体」班会議
  • Place of Presentation: 山梨県(リゾナーレ小淵沢)
  • Year and Date: 2010-05-26
• [Remarks]
  • URL: http://fsowonglab.w3.kanazawa-u.ac.jp/
• [Remarks]
  • URL: http://fsowonglab.w3.kanazawa-u.ac.jp/index.html