Structural basis for carcinogenesis and cancer metastasis by oncogene products

2009 Fiscal Year Final Research Report

• Project/Area Number: 17012009
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo (2007-2009); Tokyo Institute of Technology (2005-2006)
• Principal Investigator: NUREKI Osamu The University of Tokyo, 医科学研究所, 教授 (10272460)
• Co-Investigator(Kenkyū-buntansha): ISHITANI Ryuichiro 東京大学, 大学院・理学系研究科, 准教授 (90361568)
• Project Period (FY): 2005 – 2009
• Keywords: がん化 / がん細胞の転移 / 細胞骨格再構築 / 開口放出 / 転写因子 / 自然免疫

Research Abstract

To elucidate the mechanism of carcinogenesis, cancer metastasis and anti-tumor immune reaction, atomic structures of the player, the oncoproteins and anti-oncoproteins will be determined by X-ray crystallography. Based on the structures, new anti-cancer drug will be developed to achieve an efficient cancer treatment. For carcinogenesis, we focus on TGF-β signal under which many transcription regulatory molecules interplay for cellular development signal transduction. For cancer metastasis and invasion, we focus on proteins responsible for cytoskeleton reorganization and plasma membrane supply coupled with exocytosis. For innate immune reaction, we focus on Toll-like receptor (TLR) and its endogenous ligands, and on IRF transcriptional regulators acting mainly under the control of TLR to activate the transcription of proinflammatory cytokines and γ-interferon.

Research Products

• [Journal Article] Structure and function of a membrane component SecDF that enhances protein export (2011)
  • Author(s): T.Tsukazaki, H.Mori, Y.Echizen, R.Ishitani, S.Fukai, T.Tanaka, A.rederina, D.G.Vassylyev, T.Kohno, A.D.Maturana, K.Ito, O.Nureki
  • Journal Title: Nature in press
• [Journal Article] Structural basis for nonribosomal peptide synthesis by an aminoacyl-tRNA synthetase paralog (2011)
  • Author(s): L.Bonnefond, T.Arai, Y.Sakaguchi, T.Suzuki, R.Ishitani, O.Nureki
  • Journal Title: Proc.Natl.Acad.Sci.U.S.A. 108 Pages: 3912-3917
• [Journal Article] Crystal structure of autotaxin and insight into GPCR activation by lipid mediators (2011)
  • Author(s): H.Nishimasu, S.Okudaira, K.Hama, E.Mihara, N.Dohmae, A.Inoue, R.Ishitani, J.Takagi, J.Aoki, O.Nureki
  • Journal Title: Nat.Struct.Mol.Biol. 18 Pages: 205-212
• [Journal Article] Omnipotent role of archaeal elongation factor 1 alpha (EF1α in translational elongation and termination, and quality control of protein synthesis (2010)
  • Author(s): K.Saito, K.Kobayashi, M.Wada, I.Kikuno, A.Takusagawa, M.Mochizuki, T.Uchiumi, R.Ishitani, O.Nureki, K.Ito
  • Journal Title: Proc.Natl.Acad.Sci.U.S.A. 107 Pages: 19242-19247
• [Journal Article] Structural Basis for mRNA Surveillance by Archaeal Pelota and GTP-bound EF1? Complex (2010)
  • Author(s): K.Kobayashi, I.Kikuno, K.Kuroha, K.Saito, K.Ito, R.Ishitani, T.Inada, O.Nureki
  • Journal Title: Proc.Natl.Acad.Sci.USA. 107 Pages: 17575-17579
• [Journal Article] Mg^<2+>-dependent gating of bacterial MgtE channel underlies Mg^<2+> homeostasis (2009)
  • Author(s): M.Hattori, N.Iwase, N.Furuya, Y.Tanaka, T.Tsukazaki, R.Ishitani, M.E.Maguire, K.Ito, A.Maturana, O.Nureki
  • Journal Title: EMBO J 28 Pages: 3602-3612
• [Journal Article] Structural basis for translational fidelity ensured by tRNA lysidine synthetase (2009)
  • Author(s): K.Nakanishi, L.Bonnefond, S.Kimura, T.Suzuki, R.Ishitani, O.Nureki.
  • Journal Title: Nature 461 Pages: 1144-1148
• [Journal Article] Structural basis of novel interactions between the small-GTPase and GDI-like domains in prokaryotic FeoB iron transporter. (2009)
  • Author(s): M.Hattori, Y.Jin, H.Nishimasu, Y.Tanaka, M.Mochizuki, T.Uchiumi, R.Ishitani, K.Ito, O.Nureki.
  • Journal Title: Structure 17 Pages: 1345-1355
• [Journal Article] Structure of a tRNA-dependent kinase essential for selenocysteine decoding. (2009)
  • Author(s): Y.Araiso, R.L.Sherrer, R.Ishitani, J.M.L.Ho, D.Soll, O.Nureki.
  • Journal Title: Proc.Natl.Acad.Sci.USA. 106 Pages: 16215-16220
• [Journal Article] Structural basis of AdoMet-dependent aminocarboxypropyl transfer reaction catalyzed by tRNA-wybutosine synthesizing enzyme, TYW2. (2009)
  • Author(s): M.Umitsu, H.Nishimasu, A.Noma, T.Suzuki, R.Ishitani, O.Nureki
  • Journal Title: Proc.Natl.Acad.Sci.USA. 106 Pages: 15616-15621
• [Journal Article] Tuberous Sclerosis Tumor Suppressor Complex-like Complexes Act as GTPase-activating Proteins for Ral GTPases. (2009)
  • Author(s): R.Shirakawa, S.Fukai, M.Kawato, T.Higashi, H.Kondo, T.Ikeda, E.Nakayama, K.Okawa, O.Nureki, T.Kimura, T.Kita, H.Horiuchi.
  • Journal Title: J.Biol.Chem. 284 Pages: 21580-21588
• [Journal Article] Conserved Cysteine Residues of GidA Are Essential for Biogenesis of 5-Carboxymethylaminomethyluridine at tRNA Anticodon (2009)
  • Author(s): T.Osawa, K.Ito, H.Inanaga, O.Nureki, K.Tomita, T.Numata.
  • Journal Title: Structure. 17 Pages: 713-724
• [Journal Article] Atomic structure of a folate/FAD-dependent tRNA T54 methyltransferase (2009)
  • Author(s): H.Nishimasu, R.Ishitani, K.Yamashita, C.Iwashita, A.Hirata, H.Hori, O.Nureki
  • Journal Title: Proc.Natl.Acad.USA. 106 Pages: 8180-8185
• [Journal Article] Crystallization and preliminary X-ray diffraction analysis of GCIP/HHM transcriptional regulator (2009)
  • Author(s): A.Seto, H.Ikushima, T.Suzuki, Y.Sato, S.Fukai, K.Yuki, K.Miyazawa, K.Miyazono, R.Ishitani, O.Nureki
  • Journal Title: Acta Crystallogr.Sect.F. 65 Pages: 21-24
• [Journal Article] Pyrrolysyl-tRNA synthetase-tRNA(Pyl) structure reveals the molecular basis of orthogonality (2009)
  • Author(s): K.Nozawa, P.O'Donoghue, S.Gundllapalli, Y.Araiso, R.Ishitani, T.Umehara, D.Soll, O.Nureki
  • Journal Title: Nature 457 Pages: 1163-1167
• [Journal Article] Conformational transition of Sec machinery inferred from bacterial SecYE structures (2008)
  • Author(s): T.Tsukazaki, H.Mori, S.Fukai, R.Ishitani, T.Mori, N.Dohmae, A.Perederina, Y.Sugita, D.G.Vassylyev, K.Ito, O.Nureki
  • Journal Title: Nature 455 Pages: 988-991
• [Journal Article] Mg^<2+>-sensing mechanism of Mg^<2+> transporter MgtE probed by molecular dynamics study (2008)
  • Author(s): R.Ishitani, Y.Sugita, N.Dohmae, N.Furuya, M.Hattori, O.Nureki
  • Journal Title: Proc.Natl.Acad.USA. 105 Pages: 15393-15398
• [Journal Article] Structural basis for specific cleavage of Lys 63-linked polyubiquitin chains (2008)
  • Author(s): Y.Sato, A.Oshikawa, A.Yamagata, H.Mimura, M.Yamashita, K.Ookata, O.Nureki, K.Iwai, M.Komada, S.Fukai
  • Journal Title: Nature 455 Pages: 358-362
• [Journal Article] Biochemical Characterization of the Rho GTPase-regulated Actin Assembly by Diaphanous-related Formins, mDia1 and Daam1, in Platelets (2008)
  • Author(s): T.Higashi, T.Ikeda, R.Shirakawa, H.Kondo, M.Kawato, M.Horiguchi, T.Okuda, K.Okawa, S.Fukai, O.Nureki, T.Kita, H.Horiuchi.
  • Journal Title: J.Biol.Chem. 283 Pages: 8746-8755
• [Journal Article] Regulation of platelet dense granule secretion by the Ral GTPase-Exocyst pathway (2008)
  • Author(s): M.kawato, R.Shirakawa, H.Kondo, T.Higashi, T.Ikeda, K.Okawa, S.Fukai, O.Nureki, T.Kita, H.Horiuchi
  • Journal Title: J.Biol.Chem. 283 Pages: 166-174
• [Journal Article] Crystal structure of human DAAM1 formin homology 2 domain (2007)
  • Author(s): M.Yamashita, T.Higashi, S.Suetsugu, Y.Sato, T.Ikeda, R.Shirakawa, T.Kita, T.Takenawa, H.Horiuchi, S.Fukai, O.Nureki
  • Journal Title: Genes Cells 12 Pages: 1255-1265
• [Journal Article] Crystal structure of the MgtE Mg2+ transporter (2007)
  • Author(s): M Hattori, Y.Tanaka, S.Fukai, R.Ishitani, O.Nureki
  • Journal Title: Nature 448 Pages: 1072-1075
• [Journal Article] Crystal structure of the Sec4p・Sec2p complex in the nucleotide exchanging intermediatetate (2007)
  • Author(s): Y.Sato, S.Fukai, R.Ishitani, O.Nureki
  • Journal Title: Proc.Natl.Acad.Sci.USA 104 Pages: 8305-8310
• [Journal Article] Asymmetric coiled-coil structure with guanine nucleotide exchange activity (2007)
  • Author(s): Sato, R.Shirakawa, H.Horiuchi, N.Dohmae, S.Fukai, O.Nureki
  • Journal Title: Structure 15 Pages: 245-252
• [Journal Article] Complete crystallographic analysis of the dynamics of CCA-addition (2006)
  • Author(s): K.Tomita, R.Ishitani, S.Fukai, O.Nureki
  • Journal Title: Nature 443 Pages: 956-960
• [Journal Article] Structural basis of RNA-dependent recruitment of glutamine to the genetic code (2006)
  • Author(s): H.Oshikane, K.Sheppard, S.Fukai, Y.Nakamura, R.Ishitani, T.Numata, L.R.Sherrer, L.Feng, E.Schmitt, M.Panvert, S.Blanquet, Y.Mechulam, D.Soll, O.Nureki
  • Journal Title: Science 312 Pages: 1950-1954
• [Journal Article] Snapshots of tRNA sulfuration via an adenylated intermediate (2006)
  • Author(s): T.Numata, Y.Ikeuchi, S.Fukai, T.Suzuki, O.Nureki
  • Journal Title: Nature 442 Pages: 419-424
• [Journal Article] Structural basis for RNA unwinding by the DEAD-box protein Drosophila Vasa (2006)
  • Author(s): T.Sengoku, O.Nureki, A.Nakamura, S.Kobayashi, S.Yokoyama
  • Journal Title: Cell 125 Pages: 287-300
• [Journal Article] Structural basis for sulfur relay to RNA mediated by heterohexameric TusBCD complex (2006)
  • Author(s): T.Numata, S.Fukai, Y.Ikeuchi., T.Suzuki., O.Nureki
  • Journal Title: Structure 14 Pages: 357-366
• [Journal Article] Structural basis for anticodon recognition by methionyl-tRNA synthetase (2005)
  • Author(s): K.Nakanishi, Y.Ogiso, S.Fukai, O.Nureki
  • Journal Title: Nature Struct.Mol.Biol. 12 Pages: 931-932
• [Journal Article] Structural basis for lysidine formation by ATP pyrophosphatase accompanied with alysine-specific loop and a tRNA-recognition domain (2005)
  • Author(s): K.Nakanishi, S.Fukai, Y.Ikeuchi, A.Soma, Y.Sekine, T.Suzuki, O.Nureki
  • Journal Title: Proc.Natl.Acad.Sci.USA 21 Pages: 7487-7492
• [Presentation] Multiple conformational states of Sec machinery components implicated from bacterial SecYE crystal structure (2009)
  • Author(s): O.Nureki
  • Organizer: VIII European Symposium of The Protein Society
  • Place of Presentation: Zurich, Switzerland
  • Year and Date: 20090000
• [Presentation] 11^<th> International Congress on Amino Acids, Peptides and Proteins (2009)
  • Author(s): O.Nureki
  • Organizer: Genetic code expansion by non-canonical tRNA synthetases
  • Place of Presentation: Vienna, Austria
  • Year and Date: 20090000
• [Presentation] Crystal structure of the MgtE Mg^<2+> transporter (2008)
  • Author(s): O.Nureki
  • Organizer: Gordon Research Conference
  • Place of Presentation: CA, USA
  • Year and Date: 20080000
• [Presentation] Gating control mechanism of magnesium transporter MgtE (2008)
  • Author(s): O.Nureki
  • Organizer: The Joint 2^<nd> Pacific Rim International Conference on Protein Science
  • Place of Presentation: Cairns, Australia
  • Year and Date: 20080000
• [Presentation] Stop codon recoding mechanism revealed by the suppressor tRNAPyl and PylS complex structure (2008)
  • Author(s): O.Nureki
  • Organizer: ULP-JSPS forum
  • Place of Presentation: Strasbourg, France
  • Year and Date: 20080000
• [Presentation] Genetc code extension and establishment by aminoacyl-tRNA synthetase and tRNA modification enzymes (2008)
  • Author(s): O.Nureki
  • Organizer: aaRS2008
  • Place of Presentation: Veyrier du Lac, France
  • Year and Date: 20080000
• [Presentation] Structural basis for highly specific chemical reaction in the genetic code translation (2007)
  • Author(s): O.Nureki
  • Organizer: A Three-day Symposium on Advances in Structural Biology and Structure Prediction
  • Place of Presentation: Hyderabad, India
  • Year and Date: 20070000
• [Presentation] Structural basis for highly specific chemical reaction in the genetic code translation (2007)
  • Author(s): O.Nureki
  • Organizer: International Symposium on Chemical Biology
  • Place of Presentation: Kolkata, India
  • Year and Date: 20070000
• [Presentation] Structural Insights into Translational Quality Control (2007)
  • Author(s): O.Nureki
  • Organizer: American Society for Microbiology General 107^<th> Meeting
  • Place of Presentation: Toronto, Canada
  • Year and Date: 20070000
• [Presentation] Structural insights into the modification in the tRNA anticodon region (2007)
  • Author(s): O.Nureki
  • Organizer: FEBS-CNRS Workshop
  • Place of Presentation: Aussois, France
  • Year and Date: 20070000
• [Presentation] Structural insights into the gating control in bacterial transporters (2007)
  • Author(s): O.Nureki
  • Organizer: AsCA'07 (Plenary lecture)
  • Place of Presentation: Taipei, Taiwan
  • Year and Date: 20070000
• [Presentation] Deep knot folding of methyltransferase structures (2006)
  • Author(s): O.Nureki
  • Organizer: FASEB Summer Research Conferences
  • Place of Presentation: Vermont, USA
  • Year and Date: 20060000
• [Presentation] Structural Basis of RNA-Dependent Recruitment of Amino Acid to the Genetic Code (2006)
  • Author(s): O.Nureki
  • Organizer: International Conference on aaRSs
  • Place of Presentation: San Diego, USA
  • Year and Date: 20060000
• [Presentation] Structural biology on translation of genetic code (2005)
  • Author(s): O.Nureki
  • Organizer: The 10th Symposium on Recent Advances in Biophysics (Plenary Lecture)
  • Place of Presentation: Taipei, Taiwan(2005)
  • Year and Date: 20050000
• [Book] RNA修飾マシーナリーの時間分解能での反応機構(蛋白質核酸酵素) 51巻 (2006)
  • Author(s): 濡木理
  • Total Pages: 2596-2602
  • Publisher: 共立出版社
• [Book] 細胞の生と死を統括するアミノアシルtRNA合成酵素複合体(蛋白質核酸酵素) 50巻 (2005)
  • Author(s): 濡木理
  • Total Pages: 1264-1270
  • Publisher: 共立出版社
• [Book] RNA成熟マシーン(実験医学) 22巻 (2005)
  • Author(s): 濡木理
  • Total Pages: 43-50
  • Publisher: 羊土社
• [Remarks] ホームページ等
  • URL: http://www.nurekilab.net/