Comprehensive analysis of molecules related for antigen receptor signaling

• Project/Area Number: 16300093
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bioinformatics/Life informatics
• Research Institution: HOKKAIDO UNIVERSITY
• Principal Investigator: HATAKEYAMA Shigetsugu Hokkaido University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (70294973)
• Co-Investigator(Kenkyū-buntansha): NAKAYAMA Keiichi Kyushu University, Medical Institute of Bioregulation, Professor, 生体防御医学研究所, 教授 (80291508) ; KAMURA Takumi Nagoya University, Graduate School of Science, Professor, 大学院・理学研究科, 教授 (40333455)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥15,100,000 (Direct Cost: ¥15,100,000); Fiscal Year 2005: ¥5,800,000 (Direct Cost: ¥5,800,000); Fiscal Year 2004: ¥9,300,000 (Direct Cost: ¥9,300,000)
• Keywords: proteome / ubiquitylation / phosphorylation / lymphocyte / mass spectrometry

Research Abstract

This application is to analyze comprehensively about post-translational modification regarding to phosphorylation and ubiquitylation using affinity-chromatography. The system we analyzed is signal transduction system of antigen receptor signals in immune cells, especially phosphorylation and ubiquitylation. The purpose of this project is to clarify the down-stream signal transduction molecules comprehensively from the point of protein modifications.
Ubiquitylation and phosphorylation are implicated in the many intracellular phenomenons including signal transduction such as TCR,BCR,FcR signals. We analyze what molecules are ubiquitylated by collecting ubiquitylated proteins with anti-ubiquitin affinity chromatography. We tried to concentrate ubiquitylated proteins and ubiquitin-interacting proteins, to separate by SDS-PAGE, and to analyze these proteins by mass spectrometer. This analysis showed about 700 ubiquitin-related proteins. Furthermore we tried to concentrate tyrosine-phosphorylated proteins by anti-phosphotyrosine and to analyze these proteins by mass spectrometer. This analysis showed about 200 proteins (including novel proteins) which are related to tyrosine phosphorylation. It is significant to clarify the etiology of diseases such as autoimmune diseases and allergic diseases by connecting between protein modifications (such as phosphorylation and ubiquitylation) and activating signals by antigen receptors.

Research Products

• [Journal Article] Elmol inhibits ubiquitylation of Dock180. (2006)
  • Author(s): Makino, Y.
  • Journal Title: J Cell Sci. 119 Pages: 923-932
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Elmol inhibits ubiquitylation of Dock180. (2006)
  • Author(s): Makino, Y., Tsuda, M., Ichihara, S., Watanabe, T., Sawa, H., Nagashima, K., Hatakeyama, S., Tanaka, S
  • Journal Title: J.Cell Sci. 119 Pages: 923-932
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Targeted destruction of c-Myc by an engineered ubiquitin ligase suppresses cell transformation and tumor formation. (2005)
  • Author(s): Hatakeyama, S
  • Journal Title: Cancer Res. 65 Pages: 7874-7879
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Noncovalent SUMO-1 binding activity of thymine DNA glycosylase (TDG) is required for its SUMO-1 modification and colocalization with the promyelocytic leukemia protein(PML). (2005)
  • Author(s): Takahashi, H
  • Journal Title: J. Biol. Chem. 280 Pages: 5611-5621
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Cell surface expression of CD147/emmprin is regulated by cyclophilin 60. (2005)
  • Author(s): Pushkarsky, T.
  • Journal Title: J. Biol. Chem. 280 Pages: 27866-27871
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Mammalian E4 is required for cardiac development and maintenance ofthe nervous system. (2005)
  • Author(s): Kaneko-Oshikawa, C.
  • Journal Title: Mol. Cell. Biol. 25 Pages: 10953-10964
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Large-scale analysis of the human ubiquitin-related proteome. (2005)
  • Author(s): Matsumoto, M
  • Journal Title: Proteomics 5 Pages: 5145-5152
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Ubiquitylation and degradation of polo-like kinase SNK by hVPS18, a RING-H2 type ubiquitin ligase. (2005)
  • Author(s): Yogosawa, S.
  • Journal Title: J. Biol. Chem 280 Pages: 41619-41627
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Targeted destruction of c-Myc by an engineered ubiquitin ligase suppresses cell transformation and tumor formation. (2005)
  • Author(s): Hatakeyama S., Watanabe, M., Fujii, Y., Nakayama, K-i.
  • Journal Title: Cancer Res. 65 Pages: 7874-7879
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Title : Noncovalent SUMO-1 binding activity of thymine DNA glycosylase (TDG) is required for its SUMO-1 modification and colocalization with the promyelocytic leukemia protein (PML). (2005)
  • Author(s): Takahashi.H., Hatakeyama, S., Saitoh H., Nakayama, K-i.
  • Journal Title: J.Biol.Chem. 280 Pages: 5611-5621
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Cell surface expression of CD147/emmprin is regulated by cyclophilin 60. (2005)
  • Author(s): Pushkarsky, T., Yurchenko, V., Vanpouille, C., Brichacek, B., Vaisman, I., Hatakeyama, S., Nakayama, K.I., Sherry, B., Bukrinsky M.I.
  • Journal Title: J.Bio.Chem. 280 Pages: 27866-27871
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Mammalian E4 is required for cardiac development and maintenance o the nervous system. (2005)
  • Author(s): Kaneko-Oshikawa, C., Nakagawa, T., Yamada, M., Yoshikawa, H., Matsumoto, M., Yada, M., Hatakeyama S., Nakayama, K., Nakayama, K-i.
  • Journal Title: Mol.Cell.Biol. 25 Pages: 10953-10964
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Large-scale analysis of the human ubiquitin-related proteome. (2005)
  • Author(s): Matsumoto, M., Hatakeyama, S., Oyamada, K., Oda, Y., Nishimura, T., Nakayama, K-i.
  • Journal Title: Proteomics 5 Pages: 4145-4151
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Ubiquitylation and degradation of polo-like kinase SNK by hVPS18, a RING-H2 type ubiquitin ligase. (2005)
  • Author(s): Yogosawa, S., Hatakeyama S., Nakayama, K-i., Miyoshi, H., Kohsaka, S., Akazawa, C.
  • Journal Title: J.Biol.Chem. 280 Pages: 41619-41627
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Mapping of ubiquitination sites on target proteins. (2005)
  • Author(s): Hatakeyama, S., Matsumoto, M., Nakayama, K-i.
  • Journal Title: Methods Enzymol. 399 Pages: 277-286
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Noncovalent SUMO-1 binding activity of thymine DNA glycosylase (TDG) is required for its SUMO-1 modification and colocalization with the promyelocytic leukemia protein (PML). (2005)
  • Author(s): Takahashi.H
  • Journal Title: J.Biol.Chem. 280 Pages: 5611-5621
• [Journal Article] Cell surface expression of CD147/emmprin is regulated by cyclophilin 60. (2005)
  • Author(s): Pushkarsky, T.
  • Journal Title: J.Biol.Chem. 280 Pages: 27866-27871
• [Journal Article] Mammalian E4 is required for cardiac development and maintenance of the nervous system. (2005)
  • Author(s): Kaneko-Oshikawa, C.
  • Journal Title: Mol.Cell.Biol. 25 Pages: 10953-10964
• [Journal Article] Ubiquitylation and degradation of polo-like kinase SNK by hVPS18, a RING-H2 type ubiquitin ligase. (2005)
  • Author(s): Yogosawa, S.
  • Journal Title: J.Biol.Chem. 280 Pages: 41619-41627
• [Journal Article] Functional regulation of FEZ1 by the U-box-type ubiquitin ligase E4B contributes to neuritogenesis (2004)
  • Author(s): Okumura, F.
  • Journal Title: J. Biol. Chem. 279 Pages: 53533-53543
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Cytoplasmic ubiquitin ligase KPC regulates proteolysis of p27Kipl at G1 phase. (2004)
  • Author(s): Kamura, T.
  • Journal Title: Nature Cell Biol. 6 Pages: 1229-1235
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] U-box protein carboxyl terminus of Hsc70-interacting protein (CHIP) mediates poly-ubiquitylation preferentially on four-repeat Tau and is involved in neurodegeneration of tauopathy. (2004)
  • Author(s): Hatakeyama, S.
  • Journal Title: J. Neurochem. 91 Pages: 299-307
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] SUMO-1 modification of the synergy control motif of Ad4BP/SF-1 regulates synergistic transcription between Ad4BP/SF-1 and Sox9. (2004)
  • Author(s): Komatsu, T.
  • Journal Title: Mol. Endocrinol. 18 Pages: 2451-2462
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Subcellular expression of autoimmune regulator(AIRE) is organized in a spatiotemporal manner. (2004)
  • Author(s): Akiyoshi, H.
  • Journal Title: J. Biol. Chem. 279 Pages: 33984-33991
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7. (2004)
  • Author(s): Yada, M.
  • Journal Title: EMBO J. 22 Pages: 2116-2125
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Skp2-Mediated Degradation of p27 Regulates Progression into Mitosis. (2004)
  • Author(s): Nakayama, K.
  • Journal Title: Dev. Cell 6 Pages: 661-672
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Interaction of U-box-type ubiquitin-protein ligases(E3s) with molecular chaperones. (2004)
  • Author(s): Hatakeyama, S.
  • Journal Title: Genes Cells 5 Pages: 533-548
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] CHIP promotes proteasomal degradation of familial ALS-linked mutant SOD1 by ubiquitinating Hsp/Hsc70. (2004)
  • Author(s): Urushitani, M.
  • Journal Title: J. Neurochem. 90 Pages: 231-244
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Molecular clearance of ataxin-3 is regulated by a mammalian E4. (2004)
  • Author(s): Matsumoto, M.
  • Journal Title: EMBO J. 23 Pages: 659-669
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] AIRE, a Protein Responsible for Autoimmunity, Functions as an E3 Ubiquitin Ligase. (2004)
  • Author(s): Uchida, D.
  • Journal Title: J. Exp. Med. 199 Pages: 167-172
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] AIRE, a Protein Responsible for Autoimmunity, Functions as an E3 Ubiquitin Ligase. (2004)
  • Author(s): Tsunematsu, R.
  • Journal Title: J. Biol. Chem. 279 Pages: 9417-9423
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Functional regulation of FEZ1 by the U-box-type ubiquitin ligase E4B contributes to neuritogenesis. (2004)
  • Author(s): Okumura, F., Hatakeyama S., Matsumoto, M., Kamura, T., Nakayama, K-i.
  • Journal Title: J.Biol.Chem. 279 Pages: 53533-53543
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Cytoplasmic ubiquitin ligase KPC regulates proteolysis of p27^<Kip1> at G1 phase. (2004)
  • Author(s): Kamura, T., Hara, T., Matsumoto, M., Ishida, N., Okumura, F., Hatakeyama S., Yoshida, M., Nakayama, K., Nakayama, K-i.
  • Journal Title: Nature Cell Biol. 6 Pages: 1229-1235
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] U-box protein carboxyl terminus of Hsc70-interacting protein (CHIP) mediates poly-ubiquitylation preferentially on four-repeat Tau and is involved in neurodegeneration of tauopathy. (2004)
  • Author(s): Hatakeyama S., Matsumoto, M.Kamura, T., Murayama, M., Du-Hua Chui, D.-H., Planel, E., Takahashi, R., Nakayama, K-i., Takashima, A.
  • Journal Title: J.Neurochem. 91 Pages: 299-307
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] SUMO-1 modification of the synergy control motif of Ad4BP/SF-1 regulates synergistic transcription between Ad4BP/SF-1 and Sox9. (2004)
  • Author(s): Komatsu, T., Mizusaki, H., Mukai, T., Ogawa, H., Baba, D., Shirakawa, M., Hatakeyama, S., Nakayama K-i., Yamamoto H., Kikuchi, A., Morohashi, K.
  • Journal Title: Mol Endocronol. 18 Pages: 2451-2462
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Subcellular expression of autoimmune regulator (AIRE) is organized in a spatiotemporal manner. (2004)
  • Author(s): Akiyoshi, H., Hatakeyama, S., Pitkanen J., Mouri, Y., Dougcas, V., Kudoh, J., Tsurugaya, K., Uchida, D., Matsushima, A., Oshikawa, K., Nakayama, K-i., Shimizu N., Peterson, P., Matsumoto, M.
  • Journal Title: J.Biol.Chem. 279 Pages: 33984-33991
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7. (2004)
  • Author(s): Yada, M., Hatakeyama S., Kamura, T., Nishiyama, M., Tsunematsu, R., Imaki, H., Ishida, N., Okumura F., Nakayama, K., Nakayama, K-i.
  • Journal Title: EMBO J. 23 Pages: 2116-2125
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Skp2-Mediated Degradation of p27 Regulates Progression into Mitosis. (2004)
  • Author(s): Nakayama K., Nagahama, H., Minamishima, Y.A., Miyake, S., Ishida, N., Hatakeyama, S., Iemura, S., Natsume, T., Nakayama, K-i.
  • Journal Title: Dev.Cell 6 Pages: 661-672
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Interaction of U-box-type ubiquitin-protein ligases (E3s) with molecular chaperones. (2004)
  • Author(s): Hatakeyama S., Matsumoto, M., Yada, M., Keiichi I., Nakayama, K-i.
  • Journal Title: Genes Cells 9 Pages: 533-548
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] CHIP promotes proteasomal degradation of familial ALS-linked mutant SOD1 by ubiquitinating Hsp/Hsc70. (2004)
  • Author(s): Urushitani, M., Kurisu J., Tateno, M., Hatakeyama S., Nakayama, K-i., Kato, S., Takahashi, R.
  • Journal Title: J.Neurochem. 90 Pages: 231-244
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Molecular clearance of ataxin-3 is regulated by a mammalian E4. (2004)
  • Author(s): Matsumoto M., Yada, M., Hatakeyama, S., Ishimoto H., Tanimura, T., Tsuji, S., Kakizuka, A., Kitagawa, M., K-i.Nakayama.
  • Journal Title: EMBO J. 23 Pages: 659-669
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] AIRE, a Protein Responsible for Autoimmunity, Functions as an E3 Ubiquitin Ligase. (2004)
  • Author(s): Uchida, D., Hatakeyama, S., Matsushima, A., Han, H., Ishido, S., Hotta, H., Kudoh, J, Shimizu, N., Doucas, V., Nakayama KI., Kuroda, N., Matsumoto, M.
  • Journal Title: J.Exp.Med. 199 Pages: 167-172
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Mouse Fbw7/Sel-10/Cdc4 is required for notch degradation during vascular development. (2004)
  • Author(s): Tsunematsu, R., Nakayama, K., Oike, Y, Nishiyama, M., Ishida, N.Hatakeyama, S., Bessho, B., Kageyama, R., Suda, T., Nakayama, K-i.
  • Journal Title: J.Biol.Chem. 279 Pages: 9417-9423
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] AIRE functions as an E3 ubiquitin ligase. (2004)
  • Author(s): Uchida, D.
  • Journal Title: J.Exp.Med. 199 Pages: 167-172
• [Journal Article] Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7. (2004)
  • Author(s): Yada, M.
  • Journal Title: EMBO J. 23 Pages: 2116-2125
• [Journal Article] Cytoplasmic ubiquitin ligase KPC regulates proteolysis of p27^<Kip1> at G1 phase. (2004)
  • Author(s): Kamura, T.
  • Journal Title: Nature Cell Biol. 6 Pages: 1229-1235
• [Journal Article] Skp2-Mediated Degradation of p27 Regulates Progression into Mitosis. (2004)
  • Author(s): Nakayama, K.
  • Journal Title: Dev.Cell 6 Pages: 661-672
• [Journal Article] Large-scale analysis of the human ubiquitin-related proteome
  • Author(s): Matsumoto, M.
  • Journal Title: Proteomics (In press)
• [Book] Methods in Enzymology : Ubiquitin and Protein degradation 19. Mapping of ubiquitination sites on target proteins(pp277-286) (2005)
  • Author(s): Hatakeyama, S.
  • Total Pages: 907
  • Publisher: Academic press
  • Description: 「研究成果報告書概要(和文)」より
• [Book] Methods in Enzymology : Ubiquitin and Protein degradation 19. Mapping of ubiquitination sites on target proteins (2005)
  • Author(s): Hatakeyama, S.
  • Publisher: Academic press