Analysis of the proteolysis mechanism by nuclear receptors

• Project/Area Number: 19390014
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: University of Tsukuba
• Principal Investigator: YANAGISAWA Junn University of Tsukuba, 大学院・生命環境科学研究科, 教授 (50301114)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000); Fiscal Year 2008: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000); Fiscal Year 2007: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
• Keywords: ユビキチン / 核内レセプター / 蛋白質分解 / 転写制御 / クロマチン構造 / 核内レセプタ / 蛋白質 / TGF / 癌転移

Research Abstract

核内レセプターは、ビタミンA,Dなどの脂溶性ビタミン、性ホルモン、脂質などを結合物質とする細胞内受容体であり、多様な生理機能を制御する。
本研究者は、核内レセプターの1つである、エストロゲンレセプター(ER)を分解誘導するE3ライゲースCHIPを見出し、CHIPの発現と乳癌の増悪に負の相関があることを明らかにした。さらに、ERがエストロゲン依存的に標的蛋白質の分解を促すことにより、乳癌の転移を抑制する機能を有することを見出した。

Research Products

• [Journal Article] Estrogen inhibits TGF-{beta} signaling by promoting Smad2/3 degradation (2010)
  • Author(s): Ito I, Hanyu A, Wayama M, Goto N, Katsuno Y, Kawasaki S, Nakajima Y, Kajiro M, Komatsu Y, Fujimura A, Hirota R, Murayama A, Kimura K, Imamura T, Yanagisawa J
  • Journal Title: The Journal of biological chemistry (In press)
  • Peer Reviewed
• [Journal Article] Estrogen inhibits TGF-{beta} signaling by promoting Smad2/3 degradation (2010)
  • Author(s): Ito I, Hanyu A, Wayama M, Goto N, Katsuno Y, Kawasaki S, Nakajima Y, Kajiro M, Komatsu Y, Fujimura A, Hirota R, Murayama A, Kimura K, Imamura T, Yanagisawa J.
  • Journal Title: The Journal of biological chemistry (In press)
  • Peer Reviewed
• [Journal Article] The chromosomal association of condensin II is regulated by a noncatalytic function of PP2A (2009)
  • Author(s): Takemoto A, Maeshima K, Ikehara T, Yamaguchi K, Murayama A, Imamura S, Imamoto N, Yokoyama S, Hirano T, Watanabe Y, Hanaoka F, Yanagisawa J, Kimura K
  • Journal Title: Nature Structural & Molecular Biology Vol.16, No.12 Pages: 1302-1308
  • Peer Reviewed
• [Journal Article] The nucleolar protein NML regulates hepatic ATP levels during liver regeneration after partial hepatectomy (2009)
  • Author(s): Mikogai A, Yanagisawa J, Yasuzawa-Tanaka K, Murayama A
  • Journal Title: Biochemical and Biophysical Research Communications Vol.390, No3 Pages: 591-596
  • Peer Reviewed
• [Journal Article] KLF4 suppresses estrogen-dependent breast cancer growth by inhibiting the transcriptional activity of ERα (2009)
  • Author(s): Akaogi K, Nakajima Y, Ito I, Kawasaki S, Oie S, Murayama A, Kimura K, Yanagisawa J
  • Journal Title: Oncogene Vol.28, No32 Pages: 2894-2902
  • Peer Reviewed
• [Journal Article] The ubiquitin ligase CHIP acts as an upstream regulator of oncogenic pathways (2009)
  • Author(s): Kajiro M, Hirota R, Nakajima Y, Kawanowa K, So-ma K, Ito I, Yamaguchi Y, Ohie S, Kobayashi Y, Seino Y, Kawano M, Kawabe YI, Takei H, Hayashi S, Kurosumi M, Murayama A, Kimura K, Yanagisawa J
  • Journal Title: Nature Cell Biol Vol.11, No3 Pages: 312-319
  • Peer Reviewed
• [Journal Article] The chromosomal association of condensin II is regulated by a noncatalytic function-of PP2A (2009)
  • Author(s): Takemoto A, Maeshima K, Ikehara T, Yamaguchi K, Murayama A, Imamura S, Imamoto N, Yokoyama S, Hirano T, Watanabe Y, Hanaoka F, Yanagisawa J, Kimura K.
  • Journal Title: Nature Structural & Molecular Biology 16 Pages: 1302-1308
  • Peer Reviewed
• [Journal Article] The nucleolar protein NML regulates hepatic ATP levels during liver regeneration after partial hepatectomy (2009)
  • Author(s): Mikogai A, Yanagisawa J, Yasuzawa-Tanaka K, Murayama A.
  • Journal Title: Biochemical and Biophysical Research Communications 390 Pages: 591-596
  • Peer Reviewed
• [Journal Article] KLF4 suppresses estrogen-dependent breast cancer growth by inhibiting the transcriptional activity of Erα (2009)
  • Author(s): Akaogi K, Nakajima Y, Ito I, Kawasaki S, Oie S, Murayama A, Kimura K, Yanagisawa J.
  • Journal Title: Oncogene 28 Pages: 2894-2902
  • Peer Reviewed
• [Journal Article] The ubiquitin ligase CHIP acts as an upstream regulator of oncogenic pathways (2009)
  • Author(s): Kajiro M, Hirota R, Nakajima Y, Kawanowa K, So-ma K, Ito I, Yamaguchi Y, Ohie S, Kobayashi Y, Seino Y, Kawano M, Kawabe YI, Takei H, Hayashi S, Kurosumi M, Murayama A, Kimura K, Yanagisawa J.
  • Journal Title: Nature Cell Biol. 11 Pages: 312-319
  • Peer Reviewed
• [Journal Article] KLF4 suppresses estrogen-dependent breast cancer growth by inhibiting the transcriptional activity of ERα (2009)
  • Author(s): Akaogi K, Nakajima Y, Ito I, Kawasaki S, Oie S, Murayama A, Kimura K, Yanagisawa J.
  • Journal Title: Oncogene (In press)
  • Peer Reviewed
• [Journal Article] The ubiquitin ligase CHIP acts as an upstream regulator of oncogenic pathways (2009)
  • Author(s): Kajiro M, Hirota R, Nakajima Y, Kawanowa K, So-ma K, Ito I, Yamaguchi Y, Ohie S, Kobayashi Y, Seino Y, Kawano M, Kawabe YI, Takei H, Hayashi S, Kurosumi M, Murayama A, Kimura K, Yanagisawa J.
  • Journal Title: Nature Cell Biol 11(3) Pages: 312-319
  • Peer Reviewed
• [Journal Article] Kruppel-like factor 5 is essential for blastocyst development and the normal self-renewal of mouse ESCs (2008)
  • Author(s): Ema M, Mori D, Niwa H, Hasegawa Y, Yamanaka Y, Hitoshi S, Mimura J, Kawabe Y, Hosoya T, Morita M, Shimosato D, Uchida K, Suzuki N, Yanagisawa J, Sogawa K, Rossant J, Yamamoto M, Takahashi S, Fujii-Kuriyama Y
  • Journal Title: Cell Stem Cell Vol.3, No5 Pages: 555-567
  • Peer Reviewed
• [Journal Article] Epigenetic control of rDNA loci in response to intracellular energy status (2008)
  • Author(s): Murayama A, Ohmori K, Fujimura A, Minami H, Yasuzawa-Tanaka K, Kuroda T, Oie S, Daitoku H, Okuwaki M, Nagata K, Fukamizu A, Kimura K, Simizu T, Yanagisawa J
  • Journal Title: Cell Vol.133 Pages: 627-639
  • Peer Reviewed
• [Journal Article] PPARγ ligands suppress the feedback loop between E2F2 and cyclin-E1 (2008)
  • Author(s): Komatsu Y, Ito I, Wayama M, Fujimura A, Akaogi K, Machida H, Nakajima Y, Kuroda T, Ohmori K, Murayama A, Kimura K, Yanagisawa J
  • Journal Title: Biochem Biophys Res Commun. Vol.370,No.1 Pages: 145-148
  • Peer Reviewed
• [Journal Article] Kruppel-like factor 5 is essential for blastocyst development and the normal self-renewal of mouse ESCs (2008)
  • Author(s): Ema M, Mori D, Niwa H, Hasegawa Y, Yamanaka Y, Hitoshi S, Mimura J, Kawabe Y, Hosoya T, Morita M, Shimosato D, Uchida K, Suzuki N, Yanagisawa J, Sogawa K, Rossant J, Yamamoto M, Takahashi S, Fujii-Kuriyama Y.
  • Journal Title: Cell Stem Cell. 3(5) Pages: 555-567
  • Peer Reviewed
• [Journal Article] Epigeneticcontrol of rDNA loci in response to intracellular energy status (2008)
  • Author(s): Murayama A, Ohmori K, Fujimura A, Minami H, Yasuzawa-Tanaka K, Kuroda T, Oie S, Daitoku H, Okuwaki M, Nagata K, Fukamizu A, Kimura K, Simizu T, Yanagisawa J.
  • Journal Title: Cell. 133 Pages: 627-639
  • Peer Reviewed
• [Journal Article] Analysis of the role of Aurora B on the chromosomal targeting of condensing I. (2008)
  • Author(s): Takemoto A, Murayama A, Katano M, Urano T, Furukawa K, Yokoyama S, Yanagisawa J, Hanaoka F, Kimura K.
  • Journal Title: Nucleic Acids Res. 35 Pages: 2403-2412
  • Peer Reviewed
• [Journal Article] Kruppel-like factor 5 is essential for blastocyst development and the normal self-renewal of mouse ESCs (2008)
  • Author(s): Ema M, Mori D, Niwa H, Hasegawa Y, Yamanaka Y, Hitoshi S, Mimura J, Kawabe Y, Hosoya T, Morita M, Shimosato D, Uchida K, Suzuki N, Yanagisawa J, Sogawa K, Rossant J, Yamamoto M, Takahashi S, Fujii-Kuriyama Y.
  • Journal Title: Cell Stem Cell 3(5) Pages: 555-567
  • Peer Reviewed
• [Journal Article] Epigenetic control of rDNA loci in response to intracellular energy status (2008)
  • Author(s): Murayama A, Ohmori K, Fujimura A, Minami H, Yasuzawa-Tanaka K, Kuroda T, Oie S, Daitoku H, Okuwaki M, Nagata K, Fukamizu A, Kimura K, Simizu T, Yanagisawa J.
  • Journal Title: Cell 133 Pages: 627-639
  • Peer Reviewed
• [Journal Article] Analysis of the role of Aurora B on the chromosomal targeting of condensing I (2008)
  • Author(s): Takemoto A, Murayama A, Katano M, Urano T, Furukawa K, Yokoyama S, Yanagisawa J, Hanaoka F, Kimura K.
  • Journal Title: Nucleic Acids Res 35 Pages: 2403-2412
  • Peer Reviewed
• [Journal Article] Analysis of the role of Aurora B on the chromosomal targeting of condensing I (2007)
  • Author(s): Takemoto A, Murayama A, Katano M, Urano T, Furukawa K, Yokoyama S, Yanagisawa J, Hanaoka F, Kimura K
  • Journal Title: Nucleic Acids Res Vol.35 Pages: 2403-2412
  • Peer Reviewed
• [Presentation] 核内受容体の新しいネットワークと化学物質による制御 (2010)
  • Author(s): 柳澤純
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 就実大学(岡山県)
  • Year and Date: 2010-03-29
• [Presentation] Tumor progression and non-genomic function of nuclear receptors (2010)
  • Author(s): 柳澤純
  • Organizer: 14^<th> International Congress of Endocrinology
  • Place of Presentation: 国立京都国際会館(京都府)
  • Year and Date: 2010-03-27
• [Presentation] 核小体因子 Nucleomethylin によるエネルギー消費調節機構と細胞内エネルギー代謝 (2010)
  • Author(s): 柳澤純
  • Organizer: 生体調節研究所シンポジウム
  • Place of Presentation: 群馬大学生体調節研究所 群馬
  • Year and Date: 2010-03-17
• [Presentation] 核小体因子 Nucleomethylin によるエネルギー消費調節機構と細胞内エネルギー代謝 (2010)
  • Author(s): 柳澤純
  • Organizer: 生体調節研究所シンポジウム
  • Place of Presentation: 群馬大学生体調節研究所(群馬県)
  • Year and Date: 2010-03-17
• [Presentation] Nucleolus and Cancer (2010)
  • Author(s): 柳澤純
  • Organizer: International Conference on Radiation and Cancer Biology at Nagasaki
  • Place of Presentation: 長崎大学(長崎県)
  • Year and Date: 2010-02-18
• [Presentation] ユビキチンリガーゼCHIPプロモーターのエピゲノム情報操作による革新的乳癌治療法の開発 (2010)
  • Author(s): 柳澤純
  • Organizer: 彩都産学官連携シンポジウム
  • Place of Presentation: 千里ライフサイエンスセンター 大阪
  • Year and Date: 2010-01-14
• [Presentation] ユビキチンリガーゼCHIPプロモーターのエピゲノム情報操作による革新的乳癌治療法の開発 (2010)
  • Author(s): 柳澤純
  • Organizer: 彩都産学官連携シンポジウム
  • Place of Presentation: 千里ライフサイエンスセンター(大阪府)
  • Year and Date: 2010-01-14
• [Presentation] 核内受容体の新しいネットワークと化学物質による制御 (2010)
  • Author(s): 柳澤純
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 就実大学 岡山
• [Presentation] Nucleolus and Cancer (2010)
  • Author(s): Junn Yanagisawa
  • Organizer: Internarional Conference on Radiation and Cancer Biology at Nagasaki 2010
  • Place of Presentation: 長崎大学 長崎
• [Presentation] 核内受容体の新規機能と癌 (2009)
  • Author(s): 柳澤純
  • Organizer: 第12回 Osaka University Advanced Medical Seminar
  • Place of Presentation: 大阪大学(大阪府)
  • Year and Date: 2009-12-24
• [Presentation] Epigenetic control of rDNA loci in response to intracellular energy status (2009)
  • Author(s): 柳澤純
  • Organizer: 第32回日本分子生物学会年会ワークショップ
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2009-12-11
• [Presentation] 核内受容体によるエピゲノム制御 (2009)
  • Author(s): 柳澤純
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド(兵庫県)
  • Year and Date: 2009-10-23
• [Presentation] エネルギー代謝と肥満症 (2009)
  • Author(s): 柳澤純
  • Organizer: 第30回日本肥満学会
  • Place of Presentation: アクトシティ浜松(静岡県)
  • Year and Date: 2009-10-10
• [Presentation] 乳癌・前立腺癌における核内レセプターの新規機能とその制御 (2009)
  • Author(s): 柳澤純
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2009-10-01
• [Presentation] がんの進展とタンパク質分解 (2009)
  • Author(s): 柳澤純
  • Organizer: 千里ライフサイエンス振興財団平成21年度セミナー
  • Place of Presentation: 千里ライフサイエンスセンター 大阪
  • Year and Date: 2009-09-07
• [Presentation] がんの進展とタンパク質分解 (2009)
  • Author(s): 柳澤純
  • Organizer: 千里ライフサイエンス振興財団平成21年度セミナー
  • Place of Presentation: 千里ライフサイエンスセンター(大阪府)
  • Year and Date: 2009-09-07
• [Presentation] がんとユビキチンリガーゼ」について (2009)
  • Author(s): 柳澤純
  • Organizer: 第10回ホルモンと癌研究会
  • Place of Presentation: 艮陵会館(宮城県)
  • Year and Date: 2009-07-31
• [Presentation] 核内レセプターの新規パスウェイとがん (2009)
  • Author(s): 柳澤純
  • Organizer: 大阪大学蛋白質研究所セミナー
  • Place of Presentation: 大阪大学蛋白質研究所(大阪府)
  • Year and Date: 2009-06-28
• [Presentation] (2009)
  • Author(s): 柳澤純
  • Organizer: 第9回TCカンファレンス (興和製薬株式会社)
  • Place of Presentation: 興和製薬株式会社 東京
  • Year and Date: 2009-06-06
• [Presentation] 核内受容体の新規機能と癌 (2009)
  • Author(s): 柳澤純
  • Organizer: 第12回 Osaka University Advanced Medical Seminar
  • Place of Presentation: 大阪大学 大阪
• [Presentation] Epigenetic control of rDNA loci in response to intracellular energy status (2009)
  • Author(s): 柳澤純
  • Organizer: 第32回日本分子生物学会年会ワークショップ
  • Place of Presentation: パシフィコ横浜 横浜
• [Presentation] 核内受容体によるエピゲノム制御 (2009)
  • Author(s): 柳澤純
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド 神戸
• [Presentation] エネルギー代謝と肥満症 (2009)
  • Author(s): 柳澤純
  • Organizer: 第30回日本肥満学会
  • Place of Presentation: アクトシティ浜松 浜松
• [Presentation] 乳癌・前立腺癌における核内レセプターの新規機能とその制御 (2009)
  • Author(s): 柳澤純
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜 横浜
• [Presentation] 「がんとユビキチンリガーゼ」について (2009)
  • Author(s): 柳澤純
  • Organizer: 第10回ホルモンと癌研究会
  • Place of Presentation: 艮陵会館 仙台
• [Presentation] 核内レセプターの新規パスウェイとがん (2009)
  • Author(s): 柳澤純
  • Organizer: 大阪大学蛋白質研究所セミナー
  • Place of Presentation: 大阪大学蛋白質研究所1F講堂 吹田キャンパス
• [Presentation] 環境因子によるエピジェネティクス制御 (2009)
  • Author(s): 柳澤純
  • Organizer: 第5回宮崎サイエンスキャンプ
  • Place of Presentation: ワールドコンベンションセンター サミット宮崎
• [Presentation] 環境因子によるエピジェネティクス制御 (2009)
  • Author(s): 柳澤純
  • Organizer: 第5回宮崎サイエンスキャンプ
  • Place of Presentation: ワールドコンベンションセンター サミット宮崎(宮崎県)
• [Presentation] eNoSC, a novel protein complex, senses intracellular energy status and epigenetically controls the rDNA locus (2008)
  • Author(s): Junn Yanagisawa
  • Organizer: THE 21^<ST> NAITO CONFERENCE ON Nuclear Dynamics and RNA[I]
  • Place of Presentation: 八ヶ岳ロイヤルホテル
  • Year and Date: 2008-06-25
• [Presentation] eNoSC, a novel protein complex, senses intracellular energy status and epigenetically controls the rDNA locus (2008)
  • Author(s): 柳澤純
  • Organizer: THE 21^<ST> NAITO CONFERENCE ON Nuclear Dynamics and RNA[I]
  • Place of Presentation: 八ヶ岳ロイヤルホテル(山梨県)
  • Year and Date: 2008-06-25
• [Presentation] Estrogen enhances prostate cancer progression by inducing KLF5 degradation (2008)
  • Author(s): Junn Yanagisawa
  • Organizer: BMB2008 (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: 神戸ポートアイランド
• [Presentation] 核内レセプターの新規機能と創薬 (2007)
  • Author(s): 柳澤純
  • 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: パシフィコ横浜
  • Year and Date: 2007-12-13
• [Presentation] 核内受容体の新規機能と癌転移抑制 (2007)
  • Author(s): 柳澤純
  • Organizer: 第10回癌と骨変病研究会
  • Place of Presentation: 癌研有明病院 吉田講堂
  • Year and Date: 2007-11-17
• [Presentation] Nuclear receptor dependent protein degradation and cancer metastasis (2007)
  • Author(s): Junn Yanagisawa
  • Organizer: The 3^<rd> DECODE for Biological Responses International Meeting
  • Place of Presentation: 日本科学未来館
  • Year and Date: 2007-08-04
• [Presentation] 癌化のスイッチ～ホルモンと癌の関係～ (2007)
  • Author(s): 柳澤純
  • Organizer: 高校生と市民のための公開講座 知っておこう! 環境がゲノムに作用する仕組み～生命のスイッチ～
  • Place of Presentation: 筑波大学総合研究棟A1階110講義室
  • Year and Date: 2007-07-28
• [Remarks]
  • URL: http://yanagisawalab.org/home/