Structural basis of functional coupling between transcription and cellular metabolism

2010 Fiscal Year Final Research Report

• Project/Area Number: 18GS0316
• Research Category: Grant-in-Aid for Creative Scientific Research
• Allocation Type: Single-year Grants
• Research Institution: Osaka University
• Principal Investigator: MORIKAWA Kosuke Osaka University, 蛋白質研究所, 特任研究員(客員教授) (80012665)
• Co-Investigator(Kenkyū-buntansha): MURAYAMA Akiko 筑波大学, 生命環境科学研究科, 講師 (50431656) ; TATE Shinーichi 広島大学, 理学研究科, 教授 (20216998) ; KIMURA Keiji 筑波大学, 生命環境科学研究科, 准教授 (50332268) ; OYAMA Takuji 大阪大学, 蛋白質研究所, 特任研究員 (60423133) ; SHIRAKI Takuma 東北大学, 医学系研究科, 助教 (10311747)
• Co-Investigator(Renkei-kenkyūsha): TAKAO Toshifumi 大阪大学, 蛋白質研究所, 教授 (10197048)
• Project Period (FY): 2006 – 2010
• Keywords: ホメオスターシス / 核内受容体 / 脂質代謝物 / 蛋白質立体構造 / 転写調節因子

Research Abstract

Various "-ome" researches are currently ongoing. Although we acknowledge that these data are enormous collections for elementary pieces of biological phenomena, it remains unclear how biological system connects these pieces each other at the molecular level. In our research project, we focused on the apparently classical theme, "functional coupling between transcription and cellular metabolism". From this point of view, we have focused on nuclear receptors, and revealed the structural basis for how transcription factors monitors cellular metabolites and regulates homeostasis.

Research Products

• [Journal Article] Design, Synthesis, and Structural analysis of phenylpropanoic acid-Type PPARy-selective agonists : discovery of reversed stereochemistry-activity relationship. (2011)
  • Author(s): Ohashi, M., Oyama, T., Nakagome, I., Satoh, M., Nishino, Y., Nobusada, H., Hirono, S., Morikawa, K., Hashimoto, Y., Miyachi, H.
  • Journal Title: JMed Chem 54 Pages: 331-341
  • Peer Reviewed
• [Journal Article] Detecting structural similarity of ligand interactions in the lipid metabolic system including enzymes, lipid-binding proteins and nuclear receptors. (2011)
  • Author(s): Shionyu-Mitsuyama, C., Waku, T., Shiraki, T., Oyama, T., Shirai, T., Morikawa, K.
  • Journal Title: Protein Eng Des Sel 24 Pages: 397-403
  • Peer Reviewed
• [Journal Article] Architecture of the DNA polymerase B-proliferating cell nuclear antigen (PCNA)-DNA ternary complex. (2011)
  • Author(s): Mayanagi, K., Kiyonari, S., Nishida, H., Saito, M., Kohda, D., Ishino, Y., Shirai, T., Morikawa, K.
  • Journal Title: Proc Natl Acad Sci USA 108 Pages: 1845-1849
  • Peer Reviewed
• [Journal Article] RNA content in the nucleolus alters p53 acetylation via MYBBPIA. (2011)
  • Author(s): Kuroda, T, Murayama, A., Tatagiri, N., Ohta, Y., Fujita, E., Masumoto, H., Ema, M., Takahasi, S., Kimura, K., Yanagisawa, J.
  • Journal Title: EMBO J 30 Pages: 1054-1066
  • Peer Reviewed
• [Journal Article] Critical role of the nucleolus in activation of the p53-dependent postmitotic checkpoint. (2011)
  • Author(s): Tsuchiya, M., Katagiri, N., Kuroda, T., Kishimoto, H., Nishimura, K., Kumazawa, T., Iwasaki, N., Kimura, K., Yanagisawa, J.
  • Journal Title: Biochem Biophys Res Commun 107 Pages: 378-382
  • Peer Reviewed
• [Journal Article] Surface plasmon resonance study on functional significance of clustered organization of lectin-like oxidized LDL receptor (LOX-1). (2011)
  • Author(s): Ohki, I., Amida, H., Yamada, R., Sugihara, M., Ishigaki, T., Tate S.
  • Journal Title: Biochim Biophys Acta 1814 Pages: 345-354
  • Peer Reviewed
• [Journal Article] The nuclear receptor PPARy individually responds to serotonin-and fatty acid-metabolites. (2010)
  • Author(s): Waku, T., Shiraki, T., Oyama, T., Maebara, K., Nakamori, R., Morikawa, K.
  • Journal Title: EMBO J 29 Pages: 3395-3407
  • Peer Reviewed
• [Journal Article] Mechanism of replication machinery assembly as revealed by the DNA ligase-PCNA-DNA complex architecture. (2009)
  • Author(s): Mayanagi, K., Kiyonari, S., Saito, M., Shirai, T., Ishino, Y., Morikawa, K.
  • Journal Title: Proc Natl Acad Sci USA 106 Pages: 4647-4652.
  • Peer Reviewed
• [Journal Article] Comprehensive secondary-structure analysis of disulfide variants of lysozyme by synchrotron-radiation vacuum-ultraviolet circular dichroism. (2009)
  • Author(s): Matsuo, K., Watanabe, H., Tate, S.I., Tachibana, H., Gekko, K.
  • Journal Title: Proteins 77 Pages: 191-201
  • Peer Reviewed
• [Journal Article] Crystal structures of the Arabidopsis thaliana proliferating cell nuclear antigen 1 and 2 proteins complexed with the human p21 C-terminal segment. (2009)
  • Author(s): Strzalka, W., Oyama, T., Tori, K., Morikawa, K.
  • Journal Title: Protein Sci 18 Pages: 1072-1080
  • 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, Y.I., Takei, H., Hayashi, S., Kurosumi, M., Muravama, A., Kimura, K., Yanagisawa, J.
  • Journal Title: Nature Cell Biol. 11 Pages: 312-319
  • Peer Reviewed
• [Journal Article] Atomic structures and functional implications of the archaeal RecQ-like helicase Hjm. (2009)
  • Author(s): Oyama, T., Oka, H., Mayanagi, K., Shirai, T., Matoba, K., Fujikane, R., Ishino, Y., Morikawa, K.
  • Journal Title: BMC Struct.Biol. 9 Pages: 2
  • Peer Reviewed
• [Journal Article] Atomic structure of mutant PPARγ LBD complexed with 15d-PGJ2: novel modulation mechanism of PPARy/RXRa function by covalently bound ligands. (2009)
  • Author(s): Waku, T., Shiraki, T., Oyama, T., Morikawa, K.
  • Journal Title: FEBS Lett. 583 Pages: 320-324.
  • Peer Reviewed
• [Journal Article] Structural insight into PPARy activation through covalent modification with endogenous fatty acids. (2009)
  • Author(s): Waku, T., Shiraki, T., Oyama, T., Fujimoto, Y., Maebara, K., Kamiya, N., Jingami, H., Morikawa, K.
  • Journal Title: J Mol Biol 385 Pages: 188-199.
  • Peer Reviewed
• [Journal Article] Determination of the critical amino acids involved in the peroxisome proliferator-activated receptor (PPAR) delta selectivity of phenylpropanoic acid-derived agonists. (2008)
  • Author(s): Kasuga, J., Oyama, T., Nakagome, I., Makishima, M., Hirono, S., Morikawa, K., Hashimoto, Y., Miyachi, H.
  • Journal Title: ChemMedChem 3 Pages: 1662-1666.
  • Peer Reviewed
• [Journal Article] Improvement of the transactivation activity of phenylpropanoic acid-type peroxisome proliferator-activated receptor pan agonists : effect of introduction of fluorine at the linker part. (2008)
  • Author(s): Kasuga, J., Oyama, T., Hirakawa, Y., Makishima, M., Morikawa, K., Hashimoto, Y., Miyachi, H.
  • Journal Title: Bioorg Med Chem Lett 18 Pages: 4525-4528.
  • Peer Reviewed
• [Journal Article] Visualization of intrinsically disordered regions of proteins by high-speed atomic force microscopy. (2008)
  • Author(s): Miyagi, A., Tsunaka, Y., Uchihashi, T., Mayanagi, K., Hirose, S., Morikawa, K., Ando, T.
  • Journal Title: Chemphyschem PDME 9 Pages: 1859-1866.
  • Peer Reviewed
• [Journal Article] PPARy ligands suppress the feedback loop between E2172 and cyclin-E1. (2008)
  • Author(s): Komatsu, Y., Ito, I., Wayama, M., Fujimura, A., Akaogi, K., Machida, H., Nakajima, Y., Kuroda, T., Ohmori, K., Muravama, A., Kimura, K., Yanagisawa, J.
  • Journal Title: Biochem Biophys Res Commun 370 Pages: 145-148.
  • Peer Reviewed
• [Journal Article] Epigenetic control of rDNA loci in response to intracellular energy status. (2008)
  • Author(s): Muravama, A., Ohmori, K., Fujimura, A., Minami, H., Yasuzawa-Tanaka, K., Kuroda, T., Oie, S., Daitoku, H., Okuwaki, M., Nagata, K., Fukamizu, A., Kimura, K., Shimizu, T., Yanagisawa, J.
  • Journal Title: Cell 133 Pages: 627-629.
  • Peer Reviewed
• [Journal Article] Functional significance of octameric RuvA for a branch migration complex from Thermus thermophilus. (2008)
  • Author(s): Fujiwara, Y., Mayanagi, K., Morikawa, K.
  • Journal Title: Biochem Biophys Res Commun 366 Pages: 426-431.
  • Peer Reviewed
• [Journal Article] Anisotropic Nuclear Spin Interactions for the Morphology Analysis of Proteins in Solution by NMR Spectroscopy. (2008)
  • Author(s): Tate, S.I.
  • Journal Title: Anal Sci 24 Pages: 39-49
  • Peer Reviewed
• [Journal Article] Oxidized low-density lipoprotein receptor, LOX-1, on the endothelial cell-The receptor structure and functions of LOX-1 in atherogenesis. (2007)
  • Author(s): Tate, S.I.
  • Journal Title: J Biol Macromol 7 Pages: 11-22.
• [Journal Article] Crystal structures of autoinhibitory PDZ domain of Tamalin : implications for metabotropic glutamate receptor trafficking regulation. (2007)
  • Author(s): Sugi, T., Oyama, T., Muto, T., Nakanishi, S., Morikawa, K., Jingami, H.
  • Journal Title: EMBO J 26 Pages: 2192-2205.
  • Peer Reviewed
• [Journal Article] Analysis of the role of Aurora B on the chromosomal targeting of condensin I. (2007)
  • Author(s): Takemoto, A., Muravama, 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] Structures of the extracellular regions of the group 1I/I11 metabotropic glutamate receptors. (2007)
  • Author(s): Muto, T., Tsuchiya, D., Morikawa, K., Jingami, H.
  • Journal Title: Proc Natl Acad Sci USA 104 Pages: 3759-3764.
  • Peer Reviewed
• [Journal Article] 1α,25(OH)_2D_3-Induced Transrepression by Vitamin D Receptor through E-Box-Type Elements in the Human Parathyroid Hormone Gene Promoter. (2007)
  • Author(s): Kim M., Fujiki, R., Muravama, A., Kitagawa, H., Yamaoka, K., Yamamoto, Y., Mihara, M., Takeyama, K., Kato, S.
  • Journal Title: Mol Endocrinol 21 Pages: 334-342.
  • Peer Reviewed
• [Journal Article] Turning off estrogen receptor beta-mediated transcription requires estrogen. (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: Mol Cell Biol 26 Pages: 7966-7976
  • Peer Reviewed
• [Journal Article] The closed structure of an archaeal DNA ligase from Pyrococcus furiosus. (2006)
  • Author(s): Nishida, H., Kiyonari, S., Ishino, Y., Morikawa, K.
  • Journal Title: JMol Biol 360 Pages: 956-967.
  • Peer Reviewed
• [Presentation] The chromosomal association of condensin II by non-catalytic action of PP2A, MEXT Priority Research Project "Cell? Proliferation Control" (2009)
  • Author(s): 木村圭志.
  • Organizer: International Symposium
  • Place of Presentation: Nagoya, Japan
  • Year and Date: 2009-02-27
• [Presentation] Activation mechanism of PPARy by oxidized fatty acids. JST International Symposium (2009)
  • Author(s): 白木琢磨., 森川取右.
  • Organizer: Molecular mechanism of environmental response to food and oxygen III
  • Place of Presentation: Sendai, Japan
  • Year and Date: 2009-02-10
• [Presentation] 内在性リガンドによる核内受容体PPARγの活性化機構の解明と創薬への応用. (2009)
  • Author(s): 白木琢磨、和久剛、森川取右
  • Organizer: 転写情報DECODE・冬のワークショップ.
  • Place of Presentation: 越後湯沢.
  • Year and Date: 2009-01-19
• [Presentation] The molecular morphology analysis using the orientation induced Trosy shi changes. (2008)
  • Author(s): 楯真一
  • Organizer: 第47回NMR討論会.
  • Place of Presentation: つくば
  • Year and Date: 2008-11-13
• [Presentation] PPARy activating process through covalent modification by endogenous fatty acids. (2008)
  • Author(s): 白木琢磨.
  • Organizer: Lipid Peroxidation
  • Place of Presentation: Karuizawa, Japan
  • Year and Date: 2008-10-16
• [Presentation] Structural view of PPAR7 activating process through covalent modification by endogenous fatty acids XXII Paulo Foundation (2008)
  • Author(s): 森川取右.
  • Organizer: Symposium, INPEC
  • Place of Presentation: Naantali Spa,Finland
  • Year and Date: 2008-06-14
• [Presentation] Differential chromosomal targeting of condensins by PP2A. (2008)
  • Author(s): 木村圭志
  • Organizer: 遺伝研国際シンポジウム.
  • Place of Presentation: 伊勢
  • Year and Date: 2008-05-30
• [Presentation] 新規核小体転写制御因子NucleomethylinによるDNAメチル化制御機構. (2008)
  • Author(s): 村山明子
  • Organizer: 08遺伝情報DECODE・冬のワークショップ.
  • Place of Presentation: 南魚沼郡.
  • Year and Date: 2008-01-22
• [Presentation] Visualization of intrinsically disordered regions of proteins by high-speedatomic fbrce microscopy. (2007)
  • Author(s): 森川取右
  • Organizer: 日本生物物理学会第45回年会.
  • Place of Presentation: 横浜.
  • Year and Date: 2007-12-13
• [Presentation] The identification and characterization of a novel nucleolar protein, Nucleomethylin. (2007)
  • Author(s): 村山明子
  • Organizer: 20th Wilhelm Bernhard Workshop
  • Place of Presentation: St.Andrews, UK
  • Year and Date: 2007-08-28
• [Presentation] Structural View of the clamp-loading mechanism onto DNA. (2007)
  • Author(s): 森川取右.
  • Organizer: Albany 2007: The 15th Conversation
  • Place of Presentation: Albany, USA
  • Year and Date: 2007-06-19
• [Presentation] Structural View of metabotropic glutamate receptor activation. (2007)
  • Author(s): 森川取右.
  • Organizer: INPEC meeting
  • Place of Presentation: Jaca, Spain
  • Year and Date: 2007-06-13
• [Book] 分子生物学会編「なぜなぜ生物学」 (2010)
  • Author(s): 白木琢磨(共著)
  • Publisher: 東京化学同人
• [Book] Functional and Structural Biology on the Lipo-network (2006)
  • Author(s): Editor-in-Chief : Kosuke Morikawa, Shin-ichi Tate
  • Total Pages: ISBN-81-7895-232-7
  • Publisher: Transworld Research Network
• [Book] 化学実験講座8NMR・ESR(15節核スピン系のダイナミクス) (2006)
  • Author(s): 楯真一
  • Publisher: 日本化学会
• [Book] 化学実験講座8NMR・ESR(3.2節異種核相関) (2006)
  • Author(s): 楯真一
  • Publisher: 日本化学会
• [Patent(Industrial Property Rights)] 核内受容体に結合するリガンド (2006)
  • Inventor(s): 白木琢磨
  • Industrial Property Rights Holder: 大阪大学
  • Industrial Property Number: 特許,特願2006-117239,PCTIJP2007/056780
  • Filing Date: 20060420,20070329