Mechanism of virus infection and proliferation by an deubiquitination enzyme, AMSH

• Project/Area Number: 19590484
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: Miyagi Cancer Center Research Institute
• Principal Investigator: TANAKA Nobuyuki Miyagi Cancer Center Research Institute, 免疫学部, 部長 (60280872)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2007: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 酵素 / 蛋白質 / ユビキチン / 脱ユビキチン化 / ウイルス / HIV / VLP / C-CBL / AMSH / 感染

Research Abstract

ESCRT複合体は小胞輸送に必須の役割を果たすことが知られている。我々はESCRT(STAM)会合分子を探索し、新規分子AMSH,AMSH-LPを単離同定した。これらは輸送に関わるユビキチン修飾(K63)特異的な脱ユビキチン化酵素(DUB)である。本研究では、AMSHによる脱ユビキチン化と小胞輸送がウイルス増殖に関わる可能性を検証するため、サイトメガロウイルスおよびHIVの増殖制御機構への関与を調べた。その結果、サイトメガロウイルス感染において侵入と出芽をAMSHが制御することが示唆された。

Research Products

• [Journal Article] Loss of Hrs in the Central Nervous System Causes Accumulation of Ubiquitinated Proteins and Neurodegeneration. (2008)
  • Author(s): Tamai, K, Toyoshima, M, Tanaka, N*, Yamamoto, N, Owada, Y, Kiyonari, H, Murata K., Ueno Y., Ono M., Shimosegawa T., Yaegashi,N, Watanabe M, and Sugamura, K.
  • Journal Title: Am.J.Pathol. 173 Pages: 1806-1817
  • Peer Reviewed
• [Journal Article] c-Cbl-dependent Monoubiquitination and Lysosomal Degradation of gp130 (2008)
  • Author(s): Tanaka Y, Tanaka N*, Saeki Y, Tanaka K, Murakami M, Hirano T, Ishii N, Sugamura K.
  • Journal Title: Mol. Cell. Biol. 28 Pages: 4805-4818
  • Peer Reviewed
• [Journal Article] Endosomal sorting complex required for transport proteins in cancer pathogenesis, vesicular transport, and non-endosomal functions. (2008)
  • Author(s): Tanaka N*, Kyuuma M, Sugamura K.
  • Journal Title: Cancer Sci. 99 Pages: 1293-303
  • NAID: 10024007871
  • Peer Reviewed
• [Journal Article] Human parvovirus B19 NS1 protein modulates inflammatory signaling by activation of STAT3/PIAS3 in human endothelial cells. (2008)
  • Author(s): Duechting A, Tschope C, Kaiser H, Lamkemeyer T, Tanaka N, Aberle S, Lang F, Torresi J, Kandolf R, Bock CT.
  • Journal Title: J Virol. 82 Pages: 7942-7952
  • Peer Reviewed
• [Journal Article] Ubiquitin-independent binding of Hrs mediates endosomal sorting of the interleukin-2 receptor β-chain. (2008)
  • Author(s): Yamashita Y, Kojima K, Tsukahara T, Agawa H, Yamada K, Amano Y, Kurotori N, Tanaka N, Sugamura K, Takeshita T.
  • Journal Title: J. Cell. Sci. 121 Pages: 1727-38
  • Peer Reviewed
• [Journal Article] Loss of Hrs in the Central Nervous System Causes Accumulation of Ubiquitinated Proteins and Neurodegeneration (2008)
  • Author(s): Tamai, K, Tanaka, N, ら
  • Journal Title: Am. J. Pathol. 173 Pages: 1806-1817
  • Peer Reviewed
• [Journal Article] c-Cb1-dependent Monoubiquitination and Lysosomal Degradation of gp130 (2008)
  • Author(s): Tanaka Y, Tanaka N, ら
  • Journal Title: Mol. Cell. Biol. 28 Pages: 4805-4818
  • Peer Reviewed
• [Journal Article] Human parvovirus B19 NS1 protein modulates inflammatory signaling by activation of STAT3/PIAS3 in human endothelial cells (2008)
  • Author(s): Duechting A, Tanaka N, ら
  • Journal Title: J Virol. 82 Pages: 7942-7952
  • Peer Reviewed
• [Journal Article] Ubiquitin-independent binding of Hrs mediates endosomal sorting of the interleukin-2 receptor β-chain (2008)
  • Author(s): Yamashita Y, Tanaka N, ら
  • Journal Title: J. Cell. Sci. 121 Pages: 1727-1738
  • Peer Reviewed
• [Journal Article] Human CD4+ central and effector memory T cells produce IL-21: effect on cytokine-driven proliferation of CD4+ T cell subsets. (2007)
  • Author(s): Onoda T, Rahman M, Nara H, Araki A, Makabe K, Tsumoto K, Kumagai I, Kudo T, Ishii N, Tanaka N, Sugamura K, Hayasaka K, Asao H.
  • Journal Title: Int Immunol. 10 Pages: 1191-9
  • NAID: 10020107647
  • Peer Reviewed
• [Journal Article] Inhibition of tumor growth and metastasis by depletion of vesicular sorting protein Hrs: its regulatory role on E-cadherin and beta-catenin. (2007)
  • Author(s): Toyoshima M, Tanaka N, Aoki J, Tanaka Y, Murata K, Kyuuma M, Kobayashi H, Ishii N, Yaegashi N, Sugamura K.
  • Journal Title: Cancer Res. 67 Pages: 5162-71
  • Peer Reviewed
• [Journal Article] Role of Hrs in Maturation of Autophagosomes in Mammalian Cell. (2007)
  • Author(s): Tamai,K, Tanaka, N., Nara, A, Yamamoto,A Nakagawa, I., Yoshimori, T. Ueno, Shimosegawa, T, and Sugamura K.
  • Journal Title: Biochem Biophys Res Commun. 360 Pages: 721-7
  • Peer Reviewed
• [Journal Article] Clathrin-dependent Entry of SARS Coronavirus into Target Cells Expressing Cytoplasmic Tail-deleted ACE2. (2007)
  • Author(s): Inoue Y, Tanaka N, Tanaka Y, Inoue S, Morita K, Min Z, Hattori T, Sugamura K.
  • Journal Title: J Virol. 81 Pages: 8722-9
  • Peer Reviewed
• [Journal Article] AMSH, an ESCRT-III associated enzyme, deubiquitinates cargo on MVB/late endosomes. (2007)
  • Author(s): Kyuuma M, Kikuchi K, Kojima K, Sugawara Y, Sato M, Mano N, Goto J, Takeshita T, Yamamoto A, Sugamura K, Tanaka N.
  • Journal Title: Cell Struct Funct. 31 Pages: 159-72
  • NAID: 130004053856
  • Peer Reviewed
• [Journal Article] Human CD4+ central and effector memory T cells produce IL-21:effect on cytokine-driven prohfbration of CD4+ T cell subsets (2007)
  • Author(s): Onoda T, Tanaka N., ほか
  • Journal Title: Int Immunol. 10 Pages: 1191-1199
  • Peer Reviewed
• [Journal Article] Inhibition of tumor growth and metastasis by depletion of vesicular sorting protein Hrs:its regulatory role on E-cadherin and beta-catenin (2007)
  • Author(s): Toyoshima M, Tanaka N., ほか
  • Journal Title: Cancer Res. 67 Pages: 5162-5171
  • Peer Reviewed
• [Journal Article] Role of Hrs in Maturation of Autophagosomes in Mammalian Cell (2007)
  • Author(s): Tamai, K, Tanaka, N., ほか
  • Journal Title: Biochem Biophys Res Commun. 360 Pages: 721-727
  • Peer Reviewed
• [Journal Article] Clathrin-dependent Entry of SARS Coronavirus into Target Cells Expressing Cytoplasmic Tail-deleted ACE2 (2007)
  • Author(s): Inoue Y, Tanaka N., ほか
  • Journal Title: J Virol. 81 Pages: 8722-8729
  • Peer Reviewed
• [Journal Article] AMSH,an ESCRT-III associated enzyme,deubiquitinates cargo on MVB/late endosomes (2007)
  • Author(s): Kyuuma, Y, Tanaka, N., ほか
  • Journal Title: Cell Struct Funct. 31 Pages: 159-172
  • NAID: 130004053856
  • Peer Reviewed
• [Presentation] Negative regulation of IL-6 signaling : c-Cb1-dependent Monoubiquitination and Lysosomal Degradation of gp130 (2008)
  • Author(s): Tanaka N
  • Organizer: 第8回あわじしま感染症免疫フォーラム
  • Place of Presentation: 兵庫県淡路市夢舞台
  • Year and Date: 2008-09-09
• [Presentation] Hrs, a master regulator of protein sorting, controls tumor growth and metastasis through E-Cadherin and β-catenin. (2008)
  • Author(s): Tanaka, N. and Sugamura, K.
  • Organizer: Keystone Symposia, Wnt/β-catenin signaling in Development and Disease.
  • Place of Presentation: Keystone CO, USA
• [Presentation] Negative regulation of IL-6 signaling: c-Cbl-dependent Monoubiquitination and Lysosomal Degradation of gp130 (2008)
  • Author(s): Tanaka, N and Sugamura K.
  • Organizer: 第8回あわじしま感染症免疫フォーラム
  • Place of Presentation: 兵庫県淡路市夢舞台
• [Presentation] STAM1/2 regultate the innate immunity through TLR4 and TLR9 signaling. (2008)
  • Author(s): 井草龍太郎、村田和子、田中伸幸、石井直人、貫和敏博、菅村和夫
  • Organizer: 第38回日本免疫学会学術総会
  • Place of Presentation: 京都
• [Presentation] ACE2細胞内領域欠損受容体を介したSARS-CoV感染機構 (2007)
  • Author(s): 井上 雄喜、田中 伸幸, ほか
  • Organizer: 第55回日本ウイルス学会
  • Place of Presentation: 札幌市
  • Year and Date: 2007-10-21
• [Presentation] Hrs, a master regulator of endosomal sorting, controls HIV gag degradation (2007)
  • Author(s): Tanaka, N., Sato, M., Semura, K. and Sugamura, K.
  • Organizer: The Awaji International Forum on Infection and Immunity
  • Place of Presentation: Awaji
• [Presentation] ACE2細胞内領域欠損受容体を介したSARS-CoV感染機構 (2007)
  • Author(s): 井上雄喜、田中伸幸、田中義乃、井上真吾、森田公一、庄敏、服部俊夫、菅村和夫
  • Organizer: 第61回日本細菌学会東北市部会
  • Place of Presentation: 仙台
• [Presentation] オートファジーを介した連鎖球菌の排除におけるHrsの役割の検討 (2007)
  • Author(s): 玉井恵一、田中伸幸、上野義之、下瀬川徹、菅村和夫
  • Organizer: 第61回日本細菌学会東北市部会
  • Place of Presentation: 仙台
• [Presentation] STAM1 and STAM2 double knock out mice enhance inflammatory reaction. (2007)
  • Author(s): 井草龍太郎、村田和子、田中伸幸、石井直人、貫和敏博、菅村和夫
  • Organizer: 第61回日本細菌学会東北市部会
  • Place of Presentation: 仙台
• [Presentation] Regulation of MHC class II function by ESCRT proteins, STAM1/2 (2007)
  • Author(s): 村田和子、井草龍太郎、石井直人、田中伸幸、菅村和夫
  • Organizer: 第61回日本細菌学会東北市部会
  • Place of Presentation: 仙台
• [Presentation] Involvement of Hrs and Itch/AIP4 in the Endosomal Sorting and Degradation of TGF-β Receptor II. (2007)
  • Author(s): プルショタム・プラサイ、田中義乃、久間昌尚、村田和子、浅尾裕信、田中伸幸、菅村和夫.
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] ACE2細胞内領域欠損受容体を介したSARS-CoV感染機構 (2007)
  • Author(s): 井上雄喜、田中伸幸、田中義乃、井上真吾、森田公一、庄敏、服部俊夫、菅村和夫
  • Organizer: 第55回日本ウイルス学会学術総会
  • Place of Presentation: 札幌
• [Presentation] c-Cbl regulates IL-6 Signaling through gp130 ubiquitination (2007)
  • Author(s): 田中義乃、田中伸幸、村上正晃、平野俊夫、菅村和夫
  • Organizer: 第37回日本免疫学会学術総会
  • Place of Presentation: 東京
• [Book] 一目でわかる免疫学(第4版)
  • Author(s): 田中伸幸
  • Publisher: (株)メディカル・サイエンス・インターナショナル