Analysis of intracellular logistics by chemical biology

2012 Fiscal Year Final Research Report

• Project Area: Intracellular logistics: interdisciplinary approaches to pathophysiology of membrane traffic
• Project/Area Number: 20113008
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Keio University (2010-2012); The Institute of Physical and Chemical Research (2008-2009)
• Principal Investigator: SIMIZU Siro 慶應義塾大学, 理工学部, 准教授 (30312268)
• Co-Investigator(Kenkyū-buntansha): KONDOH Yasumitsu 独立行政法人理化学研究所, 専任研究員 (80333342)
• Project Period (FY): 2008 – 2012
• Keywords: ケミカルバイオロジー / 化合物アレイ / 細胞内ロジスティクス / がん細胞の浸潤・転移

Research Abstract

According to the request from a plan group member and a general invitation group member, chemical array and compound solution were used and it succeeded in acquisition of the interesting compounds.
Furthermore, TPh A which is the first Pirin inhibitor was able to be identified by the chemical array, and it was able to be shown clearly by using TPh A that Pirin is important for migration of melanoma cells.

Research Products

• [Journal Article] Boronic acid inhibitors of acyl protein thioesterase 1 and 2 (2013)
  • Author(s): Zimmermann, T.J., Burger, M., Tashiro, E., Kondoh, Y., Martinez, N.E., Gormer, K., Rosin-steiner, S., Shimizu, T. Ozaki, S., Mikoshiba, K., Watanabe, N., Hall, D., Vetter, I.R., Osada, H., Hedberg, C., & Waldmann, H
  • Journal Title: ChemBioChem Volume: 14 Pages: 115-122
  • DOI: doi:10.1002/cbic.201200571
  • Peer Reviewed
• [Journal Article] High-throughput screening identifies small molecule inhibitors of molecular chaperones (2013)
  • Author(s): Kondoh, Y. & Osada, H
  • Journal Title: Current Pharmaceutical Design Volume: 19 Pages: 473-492
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/22920900
  • Peer Reviewed
• [Journal Article] Determination of cathepsin V activity and intracellular trafficking by N-glycosylation (2012)
  • Author(s): Niwa, Y., Suzuki, T., Dohmae, N., Umezawa, K. & Simizu, S
  • Journal Title: FEBS Letters Volume: 586 Pages: 3601-3607
  • DOI: doi:10.1016/j.febslet.2012.08.001
  • Peer Reviewed
• [Journal Article] Inhibition of lysenin-induced hemolysis by all-E-lutein derived from the plant Dalbergia latifolia (2012)
  • Author(s): Niwa, Y., Matsui, C., Sukumwang, N., Iinuma, H., Ikeda, Y., Koyano, T., Kovitayakorn, T., Simizu, S. & Umezawa, K
  • Journal Title: Planta Medica Volume: 78 Pages: 957-961
  • DOI: doi:10.1055/s-0031-1298538
  • Peer Reviewed
• [Journal Article] Suppression of cellular invasion by glybenclamide through inhibited secretion of platelet-derived growth factor in ovarian clear cell carcinoma ES-2 cells (2012)
  • Author(s): Yasukagawa, T., Niwa, Y., Simizu, S. & Umezawa, K
  • Journal Title: FEBS Letters Volume: 586 Pages: 1504-1509
  • DOI: doi:10.1016/j.febslet.2012.04.007
  • Peer Reviewed
• [Journal Article] Involvement of NF-κB-mediated expression of galectin-3-binding protein in tumor necrosis factor-α-induced brest cancer cell adhesion (2012)
  • Author(s): Noma, N., Simizu, S., Kambayashi, Y., Kabe, Y., Suematsu, M. & Umezawa, K
  • Journal Title: Oncology Reports Volume: 27 Pages: 2080-2084
  • DOI: doi:10.3892/or.2012.1733
  • Peer Reviewed
• [Journal Article] Protein disulfide isomerase-mediated disulfide bonds regulate the gelatinolytic activity and secretion of matrix metalloproteinase-9 (2012)
  • Author(s): Khan, M. G. M., Simizu, S., Suzuki, T., Masuda, A., Muroi, M., Kawatani, M., Dohmae, N. & Osada, H
  • Journal Title: Experimental Cell Research Volume: 318 Pages: 904-914
  • DOI: doi:10.1016/j.yexcr.2012.02.021
  • Peer Reviewed
• [Journal Article] Involvement of DNA binding domain in the cellular stability and importin affinity of NF-κB component RelB (2012)
  • Author(s): Takeiri, M., Horie, K., Takahashi, D., Watanabe, M., Horie, R., Simizu, S. & Umezawa, K
  • Journal Title: Organic & Biomolecular Chemistry Volume: 10 Pages: 3053-3059
  • DOI: doi:10.1039/c2ob07104e
  • Peer Reviewed
• [Journal Article] Crystal structure of the predicted phospholipase LYPLAL1 reveals unexpected functional plasticity despite close relationship to acyl protein thioesterases (2012)
  • Author(s): Burger, M., Zimmermann, T. J., Kondoh, Y., Stege, P., Watanabe, N., Osada, H., Waldmann, H. & Vetter, I. R
  • Journal Title: Journal of Lipid Research Volume: 53 Pages: 43-50
  • DOI: doi:10.1194/jlr.M019851
  • Peer Reviewed
• [Journal Article] Xanthohumol impairs autophagosome maturation through direct inhibition of valosin-containing protein (2012)
  • Author(s): Sasazawa, Y., Kanagaki, S., Tashiro, E., Nogawa, T., Muroi, M., Kondoh, Y., Osada, H. & Imoto, M
  • Journal Title: ACS Chemical Biology Volume: 18 Pages: 892-900
  • DOI: doi:10.1021/cb200492h
  • Peer Reviewed
• [Journal Article] Cyclic lipopeptide antibiotics bind to the N-terminal domain of the prokaryotic Hsp90 to inhibit the chaperone activity (2011)
  • Author(s): Minagawa, S., Kondoh, Y., Sueoka, K., Osada, H. & Nakamoto, H
  • Journal Title: Biochemical Journal Volume: 435 Pages: 237-246
  • DOI: doi:10.1042/BJ20100743
  • Peer Reviewed
• [Journal Article] Development of a vaccinia H1-related (VHR) phosphatase inhibitor with a nonacidic phosphate-mimicking core structure (2011)
  • Author(s): Hirai, G., Tsuchiya, A., Koyama, Y., Otani, Y., Oonuma, K., Dodo, K., Simizu, S., Osada, H. & Sodeoka, M
  • Journal Title: ChemMedChem Volume: 6 Pages: 617-622
  • DOI: doi:10.1002/cmdc.201100107
  • Peer Reviewed
• [Journal Article] Discovery of a small molecule PDI inhibitor that inhibits reduction of HIV-1 envelope glycoprotein gp120 (2011)
  • Author(s): Khan, M. G. M., Simizu, S., Lai, N. S., Kawatani, M., Shimizu, T. & Osada, H
  • Journal Title: ACS Chemical Biology Volume: 6 Pages: 245-251
  • DOI: doi:10.1021/cb100387r
  • Peer Reviewed
• [Journal Article] Discovery of novel antiviral agents directed against the influenza A virus nucleoprotein using photo-cross-linked chemical arrays (2010)
  • Author(s): Hagiwara, K., Kondoh, Y., Ueda, A., Yamada, K., Goto, H., Watanabe, T., Nakata, T., Osada, H. & Aida, Y
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 394 Pages: 721-727
  • DOI: doi:10.1016/j.bbrc.2010.03.058
  • Peer Reviewed
• [Journal Article] Identification of a novel Vpr-binding compound that inhibits HIV-1 multiplication in macrophages by chemical array (2010)
  • Author(s): Hagiwara, K., Murakami, T., Xue, G., Shimizu, Y., Takeda, E., Hashimoto, Y., Honda, K., Kondoh, Y., Osada, H., Tsunetsugu-Yokota, Y. & Aida, Y
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 403 Pages: 40-45
  • DOI: doi:10.1016/j.bbrc.2010.10.107
  • Peer Reviewed
• [Journal Article] Involvement of autocrine CXCL12/CXCR4 system in the regulation of ovarian carcinoma cell invasion (2010)
  • Author(s): Miyanishi, N., Suzuki, Y., Simizu, S., Kuwabara, Y., Banno, K. & Umezawa, K
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 403 Pages: 154-159
  • DOI: doi:10.1016/j.bbrc.2010.11.007
  • Peer Reviewed
• [Journal Article] A small-molecule inhibitor shows that pirin regulates migration of melanoma cells (2010)
  • Author(s): Miyazaki, I., Simizu, S., Okumura, H., Takagi, S. & Osada, H
  • Journal Title: Nature Chemical Biology Volume: 6 Pages: 667-673
  • DOI: doi:10.1038/nchembio.423
  • Peer Reviewed
• [Journal Article] Cleavable linker for photo-cross-linked small-molecule affinity matrix (2010)
  • Author(s): Kanoh, N., Takayama, H., Honda, K., Moriya, T., Teruya, T., Simizu, S., Osada, H. & Iwabuchi, Y
  • Journal Title: Bioconjugate Chemistry Volume: 21 Pages: 182-186
  • DOI: doi:10.1021/bc900316q
  • Peer Reviewed
• [Journal Article] Deamino-hydroxy-phoslactomycin B, a biosynthetic precursor of phoslactomycin, induces myeloid differentiation in HL-60 cells (2009)
  • Author(s): Simizu, S., Teruya, T., Nogawa, T., Aono, H., Ueki, M., Uramoto, M., Kobayashi, Y. & Osada, H
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 383 Pages: 406-410
  • DOI: doi:10.1016/j.bbrc.2009.04.014
  • Peer Reviewed
• [Journal Article] On-chip fragment-based approach for discovery of high-affinity bivalent inhibitors (2009)
  • Author(s): Miyazaki, I., Simizu, S., Ishida, K. & Osada, H
  • Journal Title: ChemBioChem Volume: 10 Pages: 838-843
  • DOI: doi:10.1002/cbic.200800704
  • Peer Reviewed
• [Journal Article] Structure-affinity relationship study of bleomycins and Shble protein by use of a chemical array (2009)
  • Author(s): Miyazaki, I., Okumura, H., Simizu, S., Takahashi, Y., Kanoh, N., Muraoka, Y., Nonomura, Y. & Osada, H
  • Journal Title: ChemBioChem Volume: 10 Pages: 845-852
  • DOI: doi:10.1002/cbic.200800728
  • Peer Reviewed
• [Journal Article] RECK negatively regulates matrix metalloproteinase-9 transcription (2009)
  • Author(s): Takagi, S., Simizu, S. & Osada, H
  • Journal Title: Cancer Research Volume: 69 Pages: 1502-1508
  • DOI: doi:10.1158/0008-5472.CAN-08-2635
  • Peer Reviewed
• [Journal Article] A cell-based screening to detect inhibitors of BRAF signaling pathway (2009)
  • Author(s): Asami, Y., Mori, M., Koshino, H., Sekiyama, Y., Teruya, T., Simizu, S., Usui, T. & Osada, H
  • Journal Title: Journal of Antibiotics Volume: 62 Pages: 105-107
  • DOI: doi:10.1038/ja.2008.17
  • Peer Reviewed
• [Journal Article] Polo-like kinase 1 phosphorylates and regulates Bcl-xL during pironetin-induced apoptosis (2009)
  • Author(s): Tamura, Y., Simizu, S., Muroi, M., Takagi, S., Kawatani, M., Watanabe, N. & Osada, H
  • Journal Title: Oncogene Volume: 28 Pages: 107-116
  • DOI: doi:10.1038/onc.2008.368
  • Peer Reviewed
• [Journal Article] Robust and systematic drug screening method using chemical arrays and the protein library: identification of novel inhibitors of carbonic anhydrase II (2008)
  • Author(s): Miyazaki, I., Simizu, S., Ichimiya, H., Kawatani, M. & Osada, H
  • Journal Title: Bioscience, Biotechnology, and Biochemistry Volume: 72 Pages: 2739-2749
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/18838795
  • Peer Reviewed
• [Journal Article] Requirement of the conserved, hydrophobic C-terminus region for the activation of heparanase (2008)
  • Author(s): Lai, N. S., Simizu, S., Morisaki, D., Muroi, M. & Osada, H
  • Journal Title: Experimental Cell Research Volume: 314 Pages: 2834-2845
  • DOI: doi: 10.1016/j.yexcr.2008.07.004
  • Peer Reviewed
• [Journal Article] Inhibition of NO-induced β-cell death by novel NF-κB inhibitor (-)-DHMEQ via activation of Nrf2-ARE pathway
  • Author(s): Ogasawara, A., Simizu, S., Ito, A., Kawai, T., Saisho, Y., Takei, I. & Umezawa, K
  • Journal Title: Biochemical and Biophysical Research Communications Volume: (掲載決定)
  • DOI: doi:10.1016/j.bbrc.2013.02.062
  • Peer Reviewed
• [Journal Article] Migracins A and B, new inhibitors of cancer cell migration, produced by Streptomyces sp
  • Author(s): Arai, Y., Iinuma, H., Ikeda, Y., Igarashi, M., Hatano, M., Kinoshita, N., Ukaji, T., Simizu, S. & Umezawa, K
  • Journal Title: The Journal of Antibiotics Volume: (掲載決定)
  • DOI: doi:10.1038/ja.2012.112
  • Peer Reviewed
• [Presentation] 低分子マイクロアレイを用いたMDM2/MDMX-p53阻害剤の探索法の開発 (2013)
  • Author(s): 野口 太朗、他
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: パシフィコ横浜、神奈川県
  • Year and Date: 2013-03-29
• [Presentation] 化合物アレイによるヘッジホッグ伝達経路の阻害剤の探索 (2013)
  • Author(s): 近藤 恭光、他
  • Organizer: 日本農芸化学会2013年度大会
  • Place of Presentation: 東北大学川内北キャンパス、宮城県
  • Year and Date: 2013-03-26
• [Presentation] がん細胞にアポトーシスを誘導するアセトアミド誘導体の活性評価と作用機序解析 (2013)
  • Author(s): 河村 達郎、他
  • Organizer: 日本農芸化学会2013年度大会
  • Place of Presentation: 東北大学川内北キャンパス、宮城県
  • Year and Date: 2013-03-26
• [Presentation] Pyrrocidine Aによるミトコンドリアを介したアポトーシス誘導機構 (2013)
  • Author(s): 上杉 祥太、他
  • Organizer: 日本農芸化学会2013年度大会
  • Place of Presentation: 東北大学川内北キャンパス、宮城県
  • Year and Date: 2013-03-26
• [Presentation] 植物ホルモン・アブシジン酸の新規アゴニスト・アンタゴニスト探索 (2013)
  • Author(s): 伊藤 卓也、他
  • Organizer: 日本農芸化学会2013年度大会
  • Place of Presentation: 東北大学川内北キャンパス、宮城県
  • Year and Date: 2013-03-25
• [Presentation] Hyaluronidase1 activity and secretion are regulated by C-mannosylation (2013)
  • Author(s): Simizu, S., et al.
  • Organizer: 9th AACR-JCA Joint Conference
  • Place of Presentation: Hyatt Regency Maui、アメリカ
  • Year and Date: 2013-02-24
• [Presentation] 化合物アレイによるアミノ酸置換変異体特異的阻害剤の探索手法の開発 (2012)
  • Author(s): 近藤 恭光、他
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場他、福岡県
  • Year and Date: 2012-12-14
• [Presentation] LAP結合TGF-β活性化反応阻害物質の探索 (2012)
  • Author(s): 山本 由佳、他
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場他、福岡県
  • Year and Date: 2012-12-13
• [Presentation] p38のゲートキーパーの多様性を標的とした特異的阻害剤探索 (2012)
  • Author(s): 須藤 龍彦、他
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場他、福岡県
  • Year and Date: 2012-12-11
• [Presentation] オートファジーを制御する低分子化合物の探索 (2012)
  • Author(s): 三好 良幣、他
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場他、福岡県
  • Year and Date: 2012-12-11
• [Presentation] LAP結合TGF-β活性化反応阻害物質の探索 (2012)
  • Author(s): 山本 由佳、他
  • Organizer: 第26回肝類洞壁細胞研究会学術集会
  • Place of Presentation: ANAクラウンプラザホテル宇部、山口県
  • Year and Date: 2012-11-17
• [Presentation] Regulation of hyaluronidase1 enzymatic activity by C-mannosylation (2012)
  • Author(s): Goto, Y., et al.
  • Organizer: EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics
  • Place of Presentation: Convention Centre Dublin、アイルランド
  • Year and Date: 2012-11-09
• [Presentation] 血漿カリクレイン依存的TGF-β活性化反応阻害剤の探索 (2012)
  • Author(s): 坂田 幸大郎、他
  • Organizer: 第23回日本レチノイド研究会
  • Place of Presentation: 米子コンベンションセンター、鳥取県
  • Year and Date: 2012-10-19
• [Presentation] Induction of RelB degradation and apoptosis in adult T-cell leukemia cells by DTCM-glutarimide (2012)
  • Author(s): 伊藤あゆみ、他
  • Organizer: 第71回 日本癌学会学術総会
  • Place of Presentation: ロイトン札幌他、北海道
  • Year and Date: 2012-09-21
• [Presentation] Role of C-mannosylation on hyaluronidase1 functions (2012)
  • Author(s): 後藤祐貴、他
  • Organizer: 第71回 日本癌学会学術総会
  • Place of Presentation: ロイトン札幌他、北海道
  • Year and Date: 2012-09-19
• [Presentation] N-glycosylation regulates cathepsin L2 functions (2012)
  • Author(s): Niwa, Y., et al.
  • Organizer: The 14th International Biennial Congress of the Metastasis Research Society
  • Place of Presentation: Brisbane Convention Centre & Exhibition Centre、オーストラリア
  • Year and Date: 2012-09-04
• [Presentation] カテプシンL2の機能に与えるN-glycosylationの役割 (2012)
  • Author(s): 丹羽祐貴、他
  • Organizer: 第21回 日本がん転移学会学術集会・総会
  • Place of Presentation: オリエンタルホテル広島、広島県
  • Year and Date: 2012-07-13
• [Presentation] がん分子標的研究の今昔 (2012)
  • Author(s): 清水史郎
  • Organizer: 理研セミナー
  • Place of Presentation: 理化学研究所、埼玉県
  • Year and Date: 2012-07-13
• [Presentation] 植物性アルカロイドconophyllineによる癌細胞薬剤耐性の軽減と標的タンパク質の結合解析 (2012)
  • Author(s): 舟崎慎太郎、他
  • Organizer: 日本がん分子標的治療学会 第16回学術集会
  • Place of Presentation: 西日本総合展示場、福岡県
  • Year and Date: 2012-06-28
• [Presentation] 免疫抑制剤デオキシスパーガリンの標的分子の探索 (2012)
  • Author(s): 村橋将崇、他
  • Organizer: 日本ケミカルバイオロジー学会 第7回年会
  • Place of Presentation: 京都大学、京都府
  • Year and Date: 2012-06-07
• [Presentation] Spectomycin B1 suppresses Estrogen Receptor α-Dependent Breast Cancer Cell Growth by inhibiting a SUMO E2 Activity (2012)
  • Author(s): Ito Akihiro、他
  • Organizer: 2nd SNU-RIKEN Joint Symposium on Chemical Biology
  • Place of Presentation: Naminara Hotel、大韓民国
  • Year and Date: 2012-05-18
• [Presentation] Screening of Chemical Regulators for TGF-β Activation Reaction (2012)
  • Author(s): Sakata Kotaro、他
  • Organizer: 2nd SNU-RIKEN Joint Symposium on Chemical Biology
  • Place of Presentation: Naminara Hotel、大韓民国
  • Year and Date: 2012-05-18
• [Remarks]
  • URL: http://www.applc.keio.ac.jp/~simizu/