Regulatory roles of protein phosphorylation in cell growth and malignant transformation

2009 Fiscal Year Final Research Report

• Project/Area Number: 17013021
• 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
• Principal Investigator: YAMAMOTO Tadashi The University of Tokyo, 医科学研究所, 教授 (40134621)
• Project Period (FY): 2005 – 2009
• Keywords: 癌 / シグナル伝達 / 蛋白質 / 遺伝子 / 発現制御

Research Abstract

Receptor-tyrosine kinases play critical roles in cancer development. We identified Tob as a signaling molecule downstream of the receptor-tyrosine kinases. Through molecular and cellular biological analysis and the analysis of gene-engineered mice, we provided evidence that Tob is involved in regulation of cell proliferation, cell death, and energy metabolism by interacting with other cellular proteins such as Ndr family kinases and a large protein complex that regulates messenger RNA turn over.

Research Products

• [Journal Article] Cep72 regulates 4 localization of key centrosomal proteins and proper bipolar spindle formation. (2009)
  • Author(s): Oshimori N, Li X, Ohsugi M, Yamamoto T.
  • Journal Title: EMBO J 28 Pages: 2066-2076
  • Peer Reviewed
• [Journal Article] A novel mouse monoclonal antibody targeting ErbB2 suppresses breast cancer growth. (2009)
  • Author(s): Kawa S, Matsushita H, Ohbayashi H, Semba K, Yamamoto T.
  • Journal Title: Biochem Biophys Res Commun 384 Pages: 329-333
  • Peer Reviewed
• [Journal Article] ANA deficiency enhances BMP-induced ectopic bone formation via transcriptional events. (2009)
  • Author(s): Miyai K, Yoneda M, Hasegawa U, Toida S, Izu Y, Hiroaki H, Hayata T, Ezura Y, Mizutani S, Miyazono K, Akiyoshi K, Yamamoto T, Noda M
  • Journal Title: J Biol Chem 284 Pages: 10593-10600
  • Peer Reviewed
• [Journal Article] Deficiency of antiproliferative family protein Ana correlates with development of lung adenocarcinoma (2009)
  • Author(s): Yoneda M, Suzuki T, Nakamura T, Ajima R, Yoshida Y, Kakuta S, Sudo K, Iwakura Y, Shibutani M, Mitsumori K, Yokota J, Yamamoto T.
  • Journal Title: Cancer Sci 100 Pages: 225-232
  • Peer Reviewed
• [Journal Article] Structural basis for the antiproliferative activity of the Tob-hCaf1 complex. (2009)
  • Author(s): Horiuchi M, Takeuchi K, Noda N, Muroya N, Suzuki T, Nakamura T, Kawamura-Tsuzuku J, Takahasi T, Yamamoto T, Inagaki F
  • Journal Title: J Biol Chem 284 Pages: 13244-13255
  • Peer Reviewed
• [Journal Article] Proteasome-mediated degradation of Tob is pivotal for triggering UV-induced apoptosis. (2009)
  • Author(s): Suzuki T, Tsuzuku J, Kawakami K, Miyasaka T, Yamamoto T.
  • Journal Title: Oncogene 28 Pages: 401-11
  • Peer Reviewed
• [Journal Article] Crystal structures of human BTG2 and mouse TIS21 involved in suppression of CAF1 deadenylase activity. (2008)
  • Author(s): Yang X, Morita M, Wang H, Suzuki T, Yang W, Luo Y, Zhao C, Bartlam M, Yamamoto T, Rao Z.
  • Journal Title: Nucl Acids Res 36(21) Pages: 6872-81
  • Peer Reviewed
• [Journal Article] Osteoporotic bone formation in mice lacking tob2; involvement of Tob2 in RANK ligand expression and osteoclasts differentiation. (2008)
  • Author(s): Ajima R, Akiyama T, Usui M, Yoneda M, Yoshida Y, Nakamura T, Minowa O, Noda M, Tanaka S, Noda T, Yamamoto T.
  • Journal Title: FEBS Lett 582 Pages: 1313-1318
  • Peer Reviewed
• [Journal Article] Kid-mediated chromosome compaction ensures proper nuclear envelop formation. (2008)
  • Author(s): Ohsugi M, Adachi K, Horai R, Kakuta S, Sudo K, Kotaki H, Tokai-Nishizumi N, Sagara H, Iwakura Y, Yamamoto T.
  • Journal Title: Cell 132 Pages: 771-782
  • Peer Reviewed
• [Journal Article] Ajuba negatively regulates the Wnt signaling pathway by promoting GSK-3b-mediated phosphorylation of b-catenin. (2008)
  • Author(s): Haraguchi K, Ohsugi M, AbeY, Semba K, Akiyama T, Yamamoto T.
  • Journal Title: Oncogene 27 Pages: 274-284
  • Peer Reviewed
• [Journal Article] Interaction of anti-proliferative protein Tob with the CCR4-NOT deadenylase complex. (2008)
  • Author(s): Miyasaka T, Morita M, Ito K, Suzuki T, Fukuda H, Takeda S, Inoue J, Semba K, Yamamoto T.
  • Journal Title: Cancer Science 99 Pages: 755-761
  • Peer Reviewed
• [Journal Article] Cnot7 null mice exhibit high bone mass phenotype and modulation of BMP action. (2007)
  • Author(s): Washio-Oikawa K, Nakamura T, Usui M, Yoneda M, Ezura Y, Ishikawa I, Kazuhisa N, Noda T, Yamamoto T, Noda M.
  • Journal Title: J, Borne. Mineral Res. 22 Pages: 1217-23
  • Peer Reviewed
• [Journal Article] ZRP-1 controls Rho GTPase-mediated actin reorganization by localizing at cell-matrix and cell-cell adhesions. (2007)
  • Author(s): Bai C, Ohsugi M, Abe Y, Yamamoto T.
  • Journal Title: J. Cell Sci. 120 Pages: 2828-2837
  • Peer Reviewed
• [Journal Article] Depletion of mammalian CCR4b deadenylasetriggers increment of the p27Kip1 mRNA level and impaires cell growth. (2007)
  • Author(s): Morita M, Suzuki T, Nakamura T, Yokoyama K, Miyasaka T, Yamamoto T
  • Journal Title: Mol. Cell. Biol. 27 Pages: 4980-4990
  • Peer Reviewed
• [Journal Article] Identification of multiple SNT-binding sites on NPM-ALK oncoprotein and their involvement in cell transformation. (2007)
  • Author(s): Chikamori, M., Fujimoto, J., Tokai-Nishizumi, N., Yamamoto, T.
  • Journal Title: Oncogene 26 Pages: 2950-2954
  • Peer Reviewed
• [Journal Article] Zoospermia in mice with targeted disruption of the Brek/Lmtk2 (brain-enriched kinase/ lemur tyrosine kinase 2) gene. (2006)
  • Author(s): Kawa, S., Ito, C., Toyama, Y., Maekawa, M., Tezuka, T., Nakamura, T., Nakazawa, T., Yokoyama, K., Yoshida, N., Toshimori, K., Yamamoto, T.
  • Journal Title: Proc Natl Acad Sci USA 103 Pages: 19344-19349
  • Peer Reviewed
• [Journal Article] Degradation of Tob1 mediated by SCFSkp2-dependent ubiquitination. (2006)
  • Author(s): Hiramatsu Y, Kitagawa K, Suzuki T, Uchida C, Hattori T, Kikuchi H, Oda T, Hatakeyama S, Nakayama K I., Yamamoto T, Konno H, Kitagawa M.
  • Journal Title: Cancer Research 66 Pages: 8477-8483
  • Peer Reviewed
• [Journal Article] The Plk1 target Kizuna stabilizes mitotic centrosomes to ensure spindle bipolarity. (2006)
  • Author(s): Oshimori N, Ohsugi M, Yamamoto T.
  • Journal Title: Nature Cell Biol. 8 Pages: 1095-1101
  • Peer Reviewed
• [Journal Article] Physical and functional interaction of FYN tyrosine kinase with a brain-enriched Rho GTPase-activating protein TCGAP. (2006)
  • Author(s): Liu H, Nakazawa T, Tezuka T, Yamamoto T.
  • Journal Title: J. Biol. Chem. 281 Pages: 23611-23619
  • Peer Reviewed
• [Journal Article] Expression Analysis of LacZ gene placed in the locus of Cnot7 exhibits its activity in osteoblasts in vivo and in mineralized nodules in vitro. (2006)
  • Author(s): Washio-Okikawa K, Nakamura T, Usui M, Yoneda M, Ezura Y, Ishikawa I, Nakashima K, Yamamoto T, Noda M.
  • Journal Title: J. Cell Biochem. 99 Pages: 538-544
  • Peer Reviewed
• [Journal Article] LATS2-Ajuba complex regulatesγ-tubulin recruitment to centrosomes and spindle organization during mitosis. (2006)
  • Author(s): Abe Y, Ohsugi M, Haraguchi K, Fujimoto J, Yamamoto T.
  • Journal Title: FEBS LETTER 580 Pages: 782-788
  • Peer Reviewed
• [Journal Article] Role of the kinesin-2 family protein, KIF3, during mitosis. (2006)
  • Author(s): Haraguchi K, Hayashi T, Jimbo T, Yamamoto T, Akiyama T
  • Journal Title: J. Biol. Chem. 281 Pages: 4094-4099
  • Peer Reviewed
• [Journal Article] Phosphorylation and inactivation of Tob contributes to the progressionof papillary carcinoma of the thyroid (2005)
  • Author(s): Ito Y, Suzuki T, Yoshida H, Tomoda C, Uruno T, Takamura Y, Miya A, Kobayashi K, Matsuzuka F, Kuma K, Yamamoto T, Miyauchi A.
  • Journal Title: Cancer Lett. 220 Pages: 237-242
  • Peer Reviewed
• [Journal Article] The chromokinesin Kid is required for maintenance of proper metaphase spindle size. (2005)
  • Author(s): Abe T., Matsumura S., Katano T., Tokai-Nishizumi N, Ohsugi M, Suzuki E, Yamamoto T
  • Journal Title: Mol. Biol. Cell 16 Pages: 5455-5463
  • Peer Reviewed
• [Journal Article] A cAMP-response element binding protein-induced microRNA regulates neuronal morphogenesis. Proc. (2005)
  • Author(s): Vo N, Klein ME, Varlamova O, Keller DM, Yamamoto T, Goodman RH, Impey S.
  • Journal Title: Natl. Acad. Sci. USA 102 Pages: 16426-16431
  • Peer Reviewed
• [Presentation] Development of Novel ErbB2 Antibody and Ph-responsive Immunoliposomes Targeting ErbB2/ HER2 in Breast Cancer Cells. (2010)
  • Author(s): 仙波憲太郎
  • Organizer: International Congress of Antibodies Conference 2010
  • Year and Date: 2010-03-25
• [Presentation] CNOT1 and CNOT2 are essential for maintaining the structural integrity and the deadenylase activity of the CCR4-NOT complex. (2009)
  • Author(s): 伊藤健太郎
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-11
• [Presentation] Anti-proliferative protein Tob is relevant to RNA metabolism and facilitates the interaction between P-body and stress granule. (2009)
  • Author(s): 小川晋一
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-11
• [Presentation] Roles of CCR4-NOT deadenylase complex in spermatogenesis and energy metabolism. (2009)
  • Author(s): 山本雅
  • Organizer: KSMBMB Annual International Conference
  • Place of Presentation: 韓国(ソウル)
  • Year and Date: 2009-10-29
• [Presentation] Transducer of ErbB2, 1(TOB1)とCNOT7間相互作用の精密解析 (2008)
  • Author(s): 渡邊正人
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] Tobファミリー遺伝子anaは肺腺癌における癌抑制遺伝子候補である (2008)
  • Author(s): 米田光宏
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-30
• [Presentation] The Tob-CCR4-NOT complex reveals novel mechanisms of G1 arrest and DNA damage-induced apoptosis. (2007)
  • Author(s): 山本雅
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] Regulation of DNA damage-induced apoptosis and sensitivity to anti-cancer drug by Tob. (2007)
  • Author(s): 鈴木亨
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] Depletion of mammalian CCR4b deadenylase triggers increment of the p27 mRNA level and impairs cell growth (2007)
  • Author(s): 森田斉弘
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] Depletion of Mammalian CCR4b Deadenylase Triggers Enhancement of the p27Kip1 mRNA level and Impairs Cell Growth (2007)
  • Author(s): 森田斉弘
  • Organizer: Mechanisms and Models of Cancer Meeting
  • Place of Presentation: La Jolla, CA
  • Year and Date: 2007-08-10
• [Remarks]
  • URL: http://www.ims.u-tokyo.ac.jp/gannsig/