Regulation of DECODE system in Development

• Project/Area Number: 17054013
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: SHIBUYA Hiroshi Tokyo Medical and Dental University, 難治疾患研究所, 教授 (30261324)
• Co-Investigator(Kenkyū-buntansha): OHNISHI Junji 東京医科歯科大学, 難治疾患研究所, 准教授 (40261276) ; SATOH Kiyotoshi 東京医科歯科大学, 難治疾患研究所, 助手 (50401386) ; MORIGUCHI Tetsuo 東京医科歯科大学, 難治疾患研究所, COE拠点形成特任教員 (40323571) ; KIM Misun 東京医科歯科大学, 難治疾患研究所, 助教 (70508332)
• Project Period (FY): 2005 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥99,200,000 (Direct Cost: ¥99,200,000); Fiscal Year 2009: ¥18,300,000 (Direct Cost: ¥18,300,000); Fiscal Year 2008: ¥18,300,000 (Direct Cost: ¥18,300,000); Fiscal Year 2007: ¥20,800,000 (Direct Cost: ¥20,800,000); Fiscal Year 2006: ¥20,800,000 (Direct Cost: ¥20,800,000); Fiscal Year 2005: ¥21,000,000 (Direct Cost: ¥21,000,000)
• Keywords: NLK / シグナル / NARF / p38 / MEF2A / リン酸化 / ユビキチン化 / 頭部形成 / 結合因子 / アフリカツメガエル / Mo / TGF-βシグナル / Wntシグナル / TCF / LEF / E2-25K / E3リガーゼ / タンパク分解 / 高血圧症 / WNK1 / SPAK / OSR1 / PHAII / Na^+-Cl^-共輸送体 / NCC / NKCC2

Research Abstract

We focus on the signal transduction regulating the mechanisms of morphogenesis and organogenesis in development. To explore potential regulators of NLK function, we identified a MAPK, ubiquitin ligase and transcriptional factors as candidate proteins that physically interact with NLK. We finally provided the evidence that these factors specifically regulates NLK function required for the anterior formation in Xenopus development.

Research Products

• [Journal Article] TMEPAI, a transmembrane TGF-b-inducible protein, sequesters Smad proteins from active participation in TGF-b signaling. (2010)
  • Author(s): Watanabe, Y., Itoh, S., Goto, T., Ohnishi, E., Inamitsu, M., Itoh, F., Satoh, K., Wiercinska, E., Yang, W., Shi, L., Tanaka, A., Nakano, N., Mommaas, A M., Shibuya, H., ten Dijke, P., Kato, M.
  • Journal Title: M o l. C e l l 37 Pages: 123-134
• [Journal Article] NLK, an essential effector of anterior formation, functions downstream of p38 MAP kinase. (2010)
  • Author(s): Ohnishi, E., Goto, T., Sato, A., Kim, M., Iemura, S., Ishitani, T., Natsume, T., Ohnishi, J., Shibuya, H.
  • Journal Title: M o l. C e l l. B i o l. 30 Pages: 675-683
• [Journal Article] Nemo-like kinase (NLK) expression in osteoblastic cells and suppression of osteoblastic differentiation. (2010)
  • Author(s): Nifuji, A., Ideno, H., Ohyama, Y., Takanabe, R., Araki, R., Abe, M., Noda, M., Shibuya, H.
  • Journal Title: E x p. C e l l R e s.
• [Journal Article] TMEPAI, a transmembrane TGF-β-inducible protein, sequesters Smad proteins from active participation in TGF-β signaling (2010)
  • Author(s): Watanabe, Y., et al.
  • Journal Title: Mol.Cell 37 Pages: 123-134
  • Peer Reviewed
• [Journal Article] NLK, an essential effector of anterior formation, functions downstream of p38 MAP kinase (2010)
  • Author(s): Ohnishi, E., et al.
  • Journal Title: Mol.Cell.Biol. 30 Pages: 675-683
  • Peer Reviewed
• [Journal Article] Nemo-like kinase(NLK)expression in osteoblastic cells and suppression of osteoblastic differentiation (2010)
  • Author(s): Nifuji, A., et al.
  • Journal Title: Mol.Cell.Biol. 130 Pages: 675-683
  • Peer Reviewed
• [Journal Article] DNA demethylation in hormone-induced transcriptional derepression. (2009)
  • Author(s): Kim, M., Kondo, T., Takada, I., Youn, M. -Y., Yamamoto, Y., Takahashi, S., Matsumoto, T., Fujiyama, S., Shirode, Y., Yamaoka, I., Kitagawa, H., Takeyama, K., Shibuya, H., Ohtake, F., Kato, S.
  • Journal Title: N a t u r e 461 Pages: 1007-1012
• [Journal Article] DNA demethylation in hormone-induced transcriptional derepression (2009)
  • Author(s): Kim, M., et al.
  • Journal Title: Nature 461 Pages: 1007-1012
  • Peer Reviewed
• [Journal Article] C. elegans WNK-STE20 pathway regulates tube formation by modulating ClC channel activity. (2008)
  • Author(s): Hisamoto, N., Moriguchi, T., Urushiyama, S., Mitani, S., Shibuya, H., Matsumoto, K.
  • Journal Title: E M B O R e p. 9 Pages: 70-75
• [Journal Article] The adaptor-like protein ROG-1 is required for activation of the Ras-MAP kinase pathway and meiotic cell cycle progression in Caenorhabditis elegans. (2007)
  • Author(s): Matsubara, Y., Kawasaki, I., Urushiyama, S., Yasuda, T., Shirakata, M., Iino, Y., Shibuya, H., Yamanashi, Y.
  • Journal Title: Genes Cells 12 Pages: 407-420
• [Journal Article] Molecular pathogenesis of pseudohypoaldosteronism type II: generation and analysis of a Wnk4D561A/+ knock-in mouse model. (2007)
  • Author(s): Yang, S. -S., Morimoto, T., Rai, T., Chiga, M., Sohara, E., Ohno, M., Uchida, K., Lin, S. -H., Moriguchi, T., Shibuya, H., Kondo, Y., Sasaki, S., Uchida, S.
  • Journal Title: Cell Metabolism 5 Pages: 331-344
• [Journal Article] NLK-MEF2A signaling regulates anterior formation in Xenopus development. (2007)
  • Author(s): Satoh, K., Ohnishi, J., Sato, A., Takeyama, M., Iemura, S., Natsume, T., Shibuya, H.
  • Journal Title: Mol. Cell. Biol. 27 Pages: 7623-7630
• [Journal Article] A histone lysine methyltransferase activated by non-canonical Wnt signalling suppresses PPAR-γtransactivation. (2007)
  • Author(s): Takada, I., Mihara, M., Suzawa, M., Ohtake, F., Kobayashi, S., Igarashi, M., Youn, M. -Y., Takeyama, K., Nakamura, T., Mezaki, Y., Takezawa, S., Yogiashi, Y., Kitagawa, H., Yamada, G., Takada, S., Minami, Y., Shibuya, H., Matsumoto, K., Kato, S.
  • Journal Title: Nature Cell Biol. 9 Pages: 1273-1285
• [Journal Article] Molecular Pathogenesis of Pseudohypoaldosteronism type II: generation and analysis of a Wnk4^<D561A/+> knock-in mouse model. (2007)
  • Author(s): Yang, S.-S., et. al.
  • Journal Title: Cell Metabolism 5 Pages: 331-344
  • Peer Reviewed
• [Journal Article] NLK-MEF2A signaling regulates anterior formation in Xenop us development. (2007)
  • Author(s): Satoh, K., et. al.
  • Journal Title: Mol. Cell. Biol. 27 Pages: 7623-7630
  • Peer Reviewed
• [Journal Article] A histone lysine methyltransferase activated by non-canonical Wnt signalling suppresses PPAR-γ transactivation. (2007)
  • Author(s): Takada, I., et. al.
  • Journal Title: Nature Cell Biol. 9 Pages: 1273-1285
  • Peer Reviewed
• [Journal Article] The adaptor-like protein ROG-1 is required for activation of the Ras-MAP kinase pathway and meiotic cell cycle progression in Caenorhabditis elegans. (2007)
  • Author(s): Matsubara et al.
  • Journal Title: Genes Cells 12 Pages: 407-420
• [Journal Article] Dok-3 sequesters Grb2 and inhibits the Ras-Erk pathway downstream of protein-tyrosine kinases. (2006)
  • Author(s): Honma, M., Higuchi, O., Shirakata, M., Yasuda, T., Shibuya, H., Iemura, S., Natsume, T., Yamanashi, Y.
  • Journal Title: Genes Cells 11 Pages: 143-151
• [Journal Article] NARF, an Nemo-like kinase (NLK)-associated Ring finger protein regulates the ubiquitylation and degradation of T cell factor/Lymphoid enhancer factor (TCF/LEF). (2006)
  • Author(s): Yamada, M., Ohnishi, J., Ohkawara, B., Iemura, S., Satoh, K., Hyodo-Miura, J., Kawachi, K., Natsume, T., Shibuya, H.
  • Journal Title: J. B i o l. C h e m. 281 Pages: 20749-20760
• [Journal Article] Dok-3 sequesters Grb2 and inhibits the Ras-Erk pathway downstream of protein-tyrosine kinases. (2006)
  • Author(s): Honma et al.
  • Journal Title: Genes Cells 11 Pages: 143-151
• [Journal Article] NARF, an Nemo-like kinase (NLK)-associated Ring finger protein regulates the ubiquitylation and degradation of T cell factor/Lymphoid enhancer factor(TCF/LEF). (2006)
  • Author(s): Yamada et al.
  • Journal Title: J. Biol. Chem. 281 Pages: 20749-20760
• [Journal Article] Functions for proteinases in the ovulatory process. (2005)
  • Author(s): Ohnishi, J., Ohnishi, E., Shibuya, H., Takahashi, T.
  • Journal Title: Biochim Biophys Acta. 1751 Pages: 95-109
• [Journal Article] WNK1 regulates phosphorylation of cation-chloride-coupled cotransporters via the STE20-related kinases, SPAK and OSR1. (2005)
  • Author(s): Moriguchi, T., Urushiyama, S., Hisamoto, N., Iemura, S., Uchida, S., Natsume, T., Matsumoto, K., Shibuya, H.
  • Journal Title: J. Biol. Chem. 280 Pages: 42685-42693
• [Journal Article] WNK1 regulates phosphorylation of cation-chloride-coupled cotransporters via the STE20-related kinases, SPAK and OSR1. (2005)
  • Author(s): Moriguchi et al.
  • Journal Title: J.Biol.Chem. 280 Pages: 42685-42693
• [Journal Article] Functions for proteinases in the ovulatory process. (2005)
  • Author(s): Ohnishi et al.
  • Journal Title: Biochim Biophys Acta. 1751 Pages: 95-109
• [Journal Article] Differential roles of renin and angiotensinogen in the feto-maternal interface to the development of complications of pregnancy. (2005)
  • Author(s): Takimoto-Ohnishi et al.
  • Journal Title: Mol.Endocrinol. 19 Pages: 1361-1372
• [Journal Article] Wnt signaling regulates the sequential onset of neurogenesis and gliogenesis via induction of BMPs. (2005)
  • Author(s): Kasai et al.
  • Journal Title: Genes Cells. 10 Pages: 777-783
• [Presentation] an essential effector of anterior formation, functions downstream of p38 MAP kinase. (2009)
  • Author(s): 後藤利保、大西英理子、佐藤淳、金美善、家村俊一郎、石谷太、夏目徹、大西淳之、澁谷浩司NLK
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-11
• [Presentation] NLK, an essential effector of anterior formation, functions downstream of p38 MAP kinase (2009)
  • Author(s): 後藤利保、大西英理子、佐藤淳、金美善、家村俊一郎、石谷太、夏目徹、大西淳之、澁谷浩司
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-11
• [Presentation] リン酸化阻害剤によるダウン症治療薬開発アプローチ (2009)
  • Author(s): 小川靖、吉田実代、大西英理子、平松俊行、小野木博、澁谷浩司、細谷孝充、萩原正敏
  • Organizer: 第82回日本薬理学会年会
  • Place of Presentation: 横浜
• [Presentation] p38 MAPK-NLK経路によるXenopus前頭部形成の制御機構 (2008)
  • Author(s): 大西淳之、大西英理子、家村俊一郎、丸山剛、西頭英起、石谷太、夏目徹、澁谷浩司
  • 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: 2008-12-12
• [Presentation] Dyneinモータータンパク質結合因子Nud CはEGFRの細胞内トラフィックを制御している (2008)
  • Author(s): 慶田城迅、花房洋、家村俊一郎、夏目徹、澁谷浩司、松本邦弘
  • 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: 2008-12-12
• [Presentation] LRRKlはESCRT-0複合体と相互作用することでEGFR細胞内トラフィックを制御している (2008)
  • Author(s): 花房洋、石川光紀、澁谷浩司、駒田雅之、松本邦弘
  • 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: 2008-12-12
• [Presentation] LRRKlキナーゼ活性依存的なEGFRの細胞内トラフィッキング制御 (2008)
  • Author(s): 石川光紀、花房洋、澁谷浩司、松本邦弘
  • Organizer: 第31回日本分子生物学会年会・第81向日本生化1学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] TMEPAIによるTGF-β/アクチビンシグナル抑制機構 (2008)
  • Author(s): 伊東進、渡邊幸秀、大西英理子、佐藤清敏、澁谷浩司、加藤光保
  • 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] 線虫C.elegansをモデル系としたBAG-2-Hsc70-CHIP複合体によるROCOファミリーキナーゼLRRKの制御機構 (2008)
  • Author(s): 福島沖之、ストラヒルパストゥホフ、花房洋、家村俊一郎、夏目徹、澁谷浩司、松本邦弘、久本直毅
  • 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] DNA脱メチル化はビタミンD一位水酸化酵素遺伝子の活性型ビタミンD依存的な転写抑制解除を制御する (2008)
  • Author(s): 金美善, 近藤剛史, 延みんよん, 高田伊知郎, 武山健一, 大竹史明, 澁谷浩司, 加藤茂明
  • 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: 2008-12-10
• [Presentation] バーキンソン病原因因子LRRK2によるvimentin cage形成 (2008)
  • Author(s): Strahil Ivanov Pastuhov、花房洋、家村俊一郎、夏目徹、澁谷浩司、稲垣昌樹、松本邦弘
  • 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: 2008-12-10
• [Presentation] CRDタンパク質Corinの機能解析 (2008)
  • Author(s): 佐藤淳、Andrew Tomlinson、澁谷浩司
  • 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: 2008-12-09
• [Presentation] Hormonal control of DNA demethylation for gene activation (2008)
  • Author(s): Shigeaki Kato, Mi-sun Kim, Hiroshi Shibuya
  • Organizer: Advanced Bone and Joint Science (ABJS) Symposium-Workshop "Molecular Regulation of Bone and Cartilage"
  • Place of Presentation: 東京
  • Year and Date: 2008-12-02
• [Presentation] p38-NLKによる頭部形成制御 (2008)
  • Author(s): 澁谷浩司
  • Organizer: 第1回XCIJ首都圏支部会(XCIJ-MA)研究集会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-18
• [Presentation] ダウン症治療薬の創成 (2008)
  • Author(s): 小川靖、吉田実代、大西英理子、平松俊行、小野木博、澁谷浩司、細谷孝充、萩原正敏
  • Organizer: 第119回日本薬理学会関東部会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-04
• [Presentation] DNA demethylation for hormone-induced transcriptional derepression (2008)
  • Author(s): Mi-sun Kim, Takeshi Kondo, I chii-o Takada, Ken-ichi Takeyama and Shigeaki Kato
  • Organizer: 30^<th> American Society for Bone and Mineral Research (ASBMR)
  • Place of Presentation: Montreal, Quebec, Canada
  • Year and Date: 2008-09-11
• [Presentation] ビタミンDによる転写抑制とDNAメチル化・脱メチル化制御 (2008)
  • Author(s): 加藤茂明、金美善
  • Organizer: 第320回脂溶性ビタミン総合研究会
  • Place of Presentation: 大阪医科大学
  • Year and Date: 2008-07-18
• [Presentation] 1a, 25(OH)2D3-induced transrepression by VDR on the human CYP27 B1 gene promoter mediates the DNA methylation (2008)
  • Author(s): Shigeaki Kato, Mi-sun Kim
  • Organizer: The 21^<th> NAITO CONFERENCE, Nuclear Dynamics and RNA[I]
  • Place of Presentation: 長野
  • Year and Date: 2008-06-25
• [Presentation] DNA demethylation for hormone-induced transcriptional derepression (2008)
  • Author(s): Mi-sun Kim, Shigeaki Kato, Hiroshi Shibuya
  • Organizer: The 21^<th> NAITO CONFERENCE, Nuclear Dyna mics and RNA[I]
  • Place of Presentation: 長野
  • Year and Date: 2008-06-24
• [Presentation] 1a, 25(OH)2D3-induced transrepression by VDR on the human CYP27B1 gene promoter mediates the DNA methylation (2008)
  • Author(s): Shigeaki Kato, Mi-sun Kim
  • Organizer: ENDO 2008 (The 90th Annual Meeting o f The Endocrine Society)
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2008-06-10
• [Presentation] 「NLKと結合因子による頭部形成制御」文部科学省科学研究費助成金「特定領域研究」2領域 (2008)
  • Author(s): 澁谷浩司
  • Organizer: 合同公開シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2008-01-08
• [Presentation] Hormonal control of DNA demethylation for gene activation (2008)
  • Author(s): Shigeaki Kato, Mi-sun Kim, Hiroshi Shibuya
  • Organizer: Advanced Bone and Joint Science (ABJS) Symposium-Workshop
  • Place of Presentation: Molecular Regulation of Bone and Cartilage
• [Presentation] DNA demethylation for hormone-induced transcriptional derepression (2008)
  • Author(s): Mi-sun Kim, Shigeaki Kato, Hiroshi Shibuya
  • Organizer: The 21th NAITO CONFERENCE
  • Place of Presentation: Nuclear Dynamics and RNA[I], Japan
• [Presentation] Hsp90/Cdc37によるパーキンソン病原因因子LRRK2のキナーゼ活性制御 (2007)
  • Author(s): パストゥホフ・ストラヒル、花房洋、家村俊一郎、夏目徹、澁谷浩司、松本邦弘
  • Organizer: 第30回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] Dyneinモータータンパク質結合因子Nud CによるEGFRの細胞内トラフィック制御 (2007)
  • Author(s): 慶田城迅、花房洋、家村俊一郎、夏目徹、澁谷浩司、松本邦弘
  • Organizer: 第30回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] LRRK1によるEGFRの細胞内トラフィックの制御 (2007)
  • Author(s): 石川光紀、花房洋、澁谷浩司、松本邦弘
  • Organizer: 第30回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] LRRK1はGrb2を介したEGFRエンドサイトーシスを制御する (2007)
  • Author(s): 花房洋、石川光紀、後藤美樹、家村俊一郎、夏目徹、澁谷浩司、松本邦弘
  • Organizer: 第30回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] NLK-MEF2A経路によるXenopus前頭部形成の制御機構 (2007)
  • Author(s): 佐藤清敏
  • Organizer: 第30回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] 線虫WNK, SPAKおよびCLCチャネルによる水分排出器官の形態制御 (2006)
  • Author(s): 久本直毅、漆山誠一、森口徹生、伊藤健太郎、三谷昌平、澁谷浩司、松本邦弘
  • Organizer: 日本分子生物学会2006フォーラム
  • Place of Presentation: 名古屋
  • Year and Date: 2006-12-09
• [Presentation] 偽性低アルドステロン症2型の原因遺伝子WNK1プロテインキナーゼはSTE20様キナーゼを介してNa+-Cl-共輸送体のN末制御領域をリン酸化する。 (2005)
  • Author(s): 森口徹生、漆山誠一、久本直毅、家村俊一郎、内田信一、夏目徹、松本邦弘、澁谷浩司
  • Organizer: 第28回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2005-12-09
• [Presentation] ユビキチンリガーゼとして機能するNLK結合因子NARFによるWntシグナル制御機構。 (2005)
  • Author(s): 大西淳之、山田美里、大河原美静、澁谷浩司
  • Organizer: 第28回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2005-12-09
• [Presentation] Dishevelled/IQGAP複合体の細胞内局在制御機構。科学技術振興機構戦略的基礎研究推進事業生物の発生・分化・再生研究領域 (2005)
  • Author(s): 足達俊吾、佐藤清敏、大河原美静、家村俊一郎、夏目徹、大西淳之、澁谷浩司
  • Organizer: 第4回公開シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2005-10-04
• [Presentation] ユビキチンリガーゼとして機能するNLK結合因子NARFによるWntシグナル制御機構。科学技術振興機構戦略的基礎研究推進事業 生物の発生・分化・再生研究領域 (2005)
  • Author(s): 山田美里、大河原美静、家村俊一郎、夏目徹、大西淳之、澁谷浩司
  • Organizer: 第4回公開シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2005-10-04
• [Remarks]
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