Functional analysis of a novel Nucleolar protein complex.

• Project/Area Number: 18689902
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: University of Tsukuba
• Principal Investigator: MURAYAMA Akiko University of Tsukuba, 大学院・生命環境科学研究科, 講師 (50431656)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥26,200,000 (Direct Cost: ¥22,300,000、Indirect Cost: ¥3,900,000); Fiscal Year 2008: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000); Fiscal Year 2007: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000); Fiscal Year 2006: ¥9,300,000 (Direct Cost: ¥9,300,000)
• Keywords: 核小体 / がん治療 / クロマチン / DNAメチル化酵素 / rRNA / 癌 / 酵素 / 発現制御 / ゲノム

Research Abstract

Nucleomethylin(NML)という新規核小体蛋白質が細胞培養液中のグルコースを減らすと、ヒト培養細胞中のリボソーム合成やたんぱく質産生量が低下することを見出した。NMLは核小体に存在し、NAD依存的脱アセチル化酵素SIRT1やヒストンH3K9メチル化酵素SUV39H1と複合体を形成する。NML複合体はrDNA領域をヘテロクロマチン化することによって栄養飢餓状態でのrRNA合成抑制に働くことを明らかにした。また、NML複合体の機能破綻はエネルギーバランスの崩壊と、それに伴う細胞死を引き起こすことから、栄養飢餓による細胞死の回避に働いていることも判明した。

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] 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 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: Biochem Biophys Res Commun. 390(3) Pages: 591-596
  • 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] PPARγligands 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] Epigenetic control of rDNA loci in response to intracellular energy status (2008)
  • Author(s): Akiko Murayama, Kazuji Omori, Akiko Fujimura, Hiroshi Minami, Kayoko Yasazawa-Tanaka, Takao Kuroda, Shohei Oie, Hiroaki Daitoku, Mitsuru Okuwaki, Kyosuke Nagata, Akiyoshi Fukamizu, Keiji Kimura, Toshiyuki Shimizu, Junn Yanagisawa
  • 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. (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
• [Journal Article] Turning Off Estrogen Receptor β-Mediated Transcription Requires Estrogen-Dependent Receptor Proteolysis. (2006)
  • Author(s): Tateishi Y, Sonoo R, Sekiya Y, Sunahara N, Kawano M, Wayama M, Hirota R, Kawabe YMurayama A, Kato S, Kimura K, Yanagisawa J
  • Journal Title: Mol. Cell. Biol. Vol.26 Pages: 7966-7976
  • Peer Reviewed
• [Journal Article] A specific CpG site demethylation in the human interleukin 2 gene promoter is an epigenetic memory. (2006)
  • Author(s): Murayama A, Sakura K, Nakama M, Yasuzawa-Tanaka K, Fujita E, Tateishi Y, Wang Y, Ushijima T, Shibuya K, Kawabe Y, Yanagisawa J
  • Journal Title: EMBO J. Vol.25 Pages: 1081-1092
  • Peer Reviewed
• [Journal Article] Negative regulation of condensing 1 by CK2-mediated phosphorylation. (2006)
  • Author(s): Takemoto A, Kimura K, Yanagisawa J, Yokoyama S, Hanaoka F.
  • Journal Title: EMBO J 25 Pages: 5339-5348
• [Journal Article] Turning Off Estrogen Receptor β-Mediated Transcription Requires Estrogen-Dependent Receptor Proteolysis. (2006)
  • Author(s): Tateishi Y, Sonoo R, Sekiya Y, Sunahara N, Kawano M, Wayama M, Hirota R, Kawabe Y, Murayama A, Kato S, Kimura K, Yanagisawa J.
  • Journal Title: Molecular and Cellular Biology 26.21 Pages: 7966-7976
• [Journal Article] A specific CpG site demethylation in the human interleukin 2 gene promoter is an epigenetic memory. (2006)
  • Author(s): Murayama A, Sakura K, Nakama M, Yasuzawa-Tanaka K, Fujita E, Tateishi Y, Wang Y, Ushijima T, Shibuya K, Kawabe Y, Yanagisawa J.
  • Journal Title: EMBO J. 25 Pages: 1081-1092
• [Journal Article] An hGCN5/TRRAP histone acetyltransferase complex co-activates BRCA1 transactivation function through histone modification (2006)
  • Author(s): Oishi H, Kitagawa H, Wada O, Takezawa S, Tora L, Kouzu-Fujita M, Takada I, Yano T, Yanagisawa J, Kato S
  • Journal Title: J Biol Chem. 281(1) Pages: 20-26
• [Presentation] 核小体因子Nucleomethylinによるリボソーム合成調節機構と細胞内エネルギー代謝 (2010)
  • Author(s): 村山明子
  • Organizer: 2010年度日本農芸化学会シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2010-03-30
• [Presentation] 核小体因子Nucleomethylinによるリボソーム合成調節機構と細胞内エネルギー代謝 (2010)
  • Author(s): 村山明子
  • Organizer: 2010年度 日本農芸化学会シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2010-03-30
• [Presentation] マウス肝臓における核小体因子Nucleomethylinの機能解析 (2009)
  • Author(s): 御子貝綾、村山明子、安澤(田中)加代子、柳澤純
  • Organizer: 第32回日本分子生物学会年会・横浜
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-12
• [Presentation] エピジェネティック機構を介した細胞内エネルギー代謝制御 (2009)
  • Author(s): 村山明子
  • Organizer: 日本レチノイド研究会第20回学術集会・ランチョンセミナー
  • Place of Presentation: 東京
  • Year and Date: 2009-11-21
• [Presentation] エピジェネティック機構を介した細胞内エネルギー代謝制御 (2009)
  • Author(s): 村山明子
  • Organizer: 日本レチノイド研究会第20回学術集会・ランチョンセミナー・東京
  • Place of Presentation: 東京
  • Year and Date: 2009-11-21
• [Presentation] 核小体因子Nucleomethylinによる核内反応制御機構の解析 (2009)
  • Author(s): 村山明子
  • Organizer: 第82回日本生化学会大会シンポジウム
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-23
• [Presentation] 核小体因子Nucleomethylinによる核内反応制御機構の解析 (2009)
  • Author(s): 村山明子
  • Organizer: 第82回日本生化学会大会 シンポジウム
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-23
• [Presentation] rDNA領域のエピジェネティックな制御による細胞内エネルギー調節機構 (2008)
  • Author(s): 村山明子
  • 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・シンポジウム
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] rDNA領域のエピジェネティックな制御による細胞内エメルギー調節機構 (2008)
  • Author(s): 村山明子
  • 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・シンポジウム
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] a novel protein complex, senses intracellular energy status and epigenetically controls the rDNA locus. (2008)
  • Author(s): Akiko Murayama, Kazuji Ohmori, Akiko Fujimura, Kayoko Yasuzawa-Tanaka, Shohei Oie, Toshiyuki Shimizu, Junn Yanagisawa eNoSC
  • Organizer: 第21回内藤コンファレンス
  • Place of Presentation: 八ヶ岳
  • Year and Date: 2008-06-26
• [Presentation] eNoSC, a novel protein comples, senses intracellular energy status and epigenetically controls the rDNA locus. (2008)
  • Author(s): Akiko Murayama, Kazuji Ohmori, Akiko Fujimura, Kayoko Yasuzawa-Tanaka, Shohei Oie, Toshiyuki Shimizu, Junn Yanagisawa
  • Organizer: 第21回内藤コンファレンス
  • Place of Presentation: 八ヶ岳
  • Year and Date: 2008-06-26
• [Presentation] a novel protein complex (2008)
  • Author(s): Akiko Murayama, Kazuji Ohmori, Akiko Fujimura, Kayoko Yasuzawa-Tanaka, Takao Kuroda, Shohei Oie, Toshiyuki Shimizu, Junn Yanagisawa eNoSC
  • Organizer: epigenetically controls the rDNA locus Metabolic Pathways of Longevity・Keystone Symposium
  • Place of Presentation: Denver
  • Year and Date: 2008-04-01
• [Presentation] eNoSC, a novel protein complex, senses intracllilar energy status and epigenetically controls the rDNA locus. (2008)
  • Author(s): Akiko Murayama, Kazuji Ohmori, Akiko Fujimura, Kayoko Yasuzawa-Tanaka, Takao Kuroda, Shohei Oie, Toshiyuki Shimizu and Junn Yanagisawa
  • Organizer: Metabolic Pathways of Longevity・Keystone Symposium
  • Place of Presentation: Denver, アメリカ
  • Year and Date: 2008-04-01
• [Book] 代謝ストレス応答とrRNA転写制御機構 (2009)
  • Author(s): 村山明子
  • Total Pages: 9
  • Publisher: 生化学 第81巻第6号p456-464
• [Remarks]
  • URL: http://yanagisawalab.org/
• [Remarks]
  • URL: http://yanagisawalab.org/home/