Analyses of reverse membrane invaginations regulated by ubiquitination-dependent mechanism

• Project/Area Number: 21590064
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Kyushu University
• Principal Investigator: FUJITA Hideaki 九州大学, 大学院・薬学研究院, 助教 (80291524)
• Co-Investigator(Renkei-kenkyūsha): TOKUNAGA Kenzo 国立感染症研究所, 感染病理部, 主任研究官 (50342895)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: リソソーム / ユビキチン / タンパク質分解 / 小胞輸送 / エンドソーム / トランスフェリン受容体 / 鉄代謝 / 細胞質分裂 / 蛋白質分解 / プロテオリシス

Research Abstract

We found a novel mechanism of down-regulation of transferring receptor. We characterized an intracellular logistics of BST-2/Tetherin, which is a host restriction factor of retrovirus. We found that Vpu, an accessory protein of HIV-1, counteracts a role of BST-2/Tetherin. We further analyzed the mechanisms of two novel whitening reagents in melanocytes.

Research Products

• [Journal Article] Intracellular logistics of BST-2/Tetherin (2012)
  • Author(s): H. Fujita, K. Fujimoto, K. Tokunaga and Y. Tanaka.
  • Journal Title: Curr HIV Res
  • Peer Reviewed
• [Journal Article] Intracellular logistics of BST-2/tetherin (2012)
  • Author(s): H.Fujita, et.al.
  • Journal Title: Current HIV Research Volume: (In press)
  • Peer Reviewed
• [Journal Article] Proteome of ubiquitin/MVB-Pathway : Possible involvement of Iron-induced ubiquitylation of transferrin receptor in lysosomal degradation (2011)
  • Author(s): R. Tachiyama, D. Ishikawa, M. Matsumoto, K. I Nakayama, T. Yoshimori, S. Yokota, M. Himeno, Y. Tanaka and H. Fujita*
  • Journal Title: Genes to Cells Volume: 16 Pages: 448-466
  • Peer Reviewed
• [Journal Article] Inhibitory effects of 16-hydroxy-9-oxo-10E, 12E, 14E-octade catrienoic acid(Corchorifatty acid B) isolated from Melissa officinalis Linne on melanogenesis. (2011)
  • Author(s): H. Fujita, M. Hongo, M. Mochizuki, K. Yokoyama and Y. Tanaka.
  • Journal Title: Experimental Dermatology Volume: 20 Pages: 420-424
  • Peer Reviewed
• [Journal Article] Inhibitory effects of 16-hydroxy-9-oxo-10E, 12E, 14E-octadecatrienoic acid (Corchorifatty acid B) isolated from Melissa officinalis Linne on melanogenesis (2011)
  • Author(s): H.Fujita, et.al.
  • Journal Title: Experimental Dermatology Volume: 20 Issue: 5 Pages: 420-424
  • DOI: 10.1111/j.1600-0625.2010.01241.x
  • Peer Reviewed
• [Journal Article] Differential Anti-APOBEC3G Activity of HIV-1 Vif Proteins Derived from Different Subtypes (2010)
  • Author(s): Y. Iwabu, M. Kinomoto, M. Tatsumi, H. Fujita, M. Shimura, Y. Tanaka, Y. Ishizaka, D. Nolan, S. Mallal, T. Sata, and K. Tokunaga.
  • Journal Title: J. Biol. Chem Volume: 285 Pages: 35350-35358
  • Peer Reviewed
• [Journal Article] Nedd4-interactin protein 2(NDFIP2), a short half-life lysosomal membrane protein (2010)
  • Author(s): C. Ohzono, S. Etoh, M. Matsumoto, K. I. Nakayama, Y. Hirota, Y. Tanaka and H. Fujita§
  • Journal Title: Biol. Pharm. Bull Volume: 33 Pages: 951-957
  • Peer Reviewed
• [Journal Article] "Direct internalization of cell-surface BST-2/tetherin by the HIV-1 accessory protein Vpu (2010)
  • Author(s): Y. Iwabu, H. Fujita, Y. Tanaka, T. Sata, and K. Tokunaga.
  • Journal Title: Communicative & Integrative Biology Pages: 366-369
  • Peer Reviewed
• [Journal Article] Nedd4-interactin protein 2 (NDFIP2), a short half-life lysosomal membrane protein, negatively controls down-regulation of connexin43 (2010)
  • Author(s): C.Ohzono, S.Etoh, M.Matsumoto, K.I.Nakayama, Y.Hirota, Y.Tanaka, H.Fujita
  • Journal Title: Biol.Pharm.Bull. Volume: 33 Pages: 951-957
  • Peer Reviewed
• [Journal Article] Differential Anti-APOBEC3G Activity of HIV-1 Vif Proteins Derived from Different Subtypes (2010)
  • Author(s): Y.Iwabu, M.Kinomoto, M.Tatsumi, H.Fujita, M.Shimura, Y.Tanaka, Y.Ishizaka, D.Nolan, S.Mallal, T.Sata, K.Tokunaga
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 35350-35358
  • Peer Reviewed
• [Journal Article] Direct internalization of cell-surface BST-2/tetherin by the HIV-1 accessory protein Vpu (2010)
  • Author(s): Y.Iwabu, H.Fujita, Y.Tanaka, Y., T.Sata, K.Tokunaga
  • Journal Title: Communicative & Integrative Biology Volume: 3 Pages: 366-369
  • Peer Reviewed
• [Journal Article] Direct internalization of cell-surface BST-2/tetherin by the HIV-1 accessory protein Vpu (2010)
  • Author(s): Iwabu, H.Fujita, Y.Tanaka, T.Sata, K.Tokunaga
  • Journal Title: Communicative & Integrative Biology 3(In press)
  • Peer Reviewed
• [Journal Article] Nedd4-interactin protein 2 (NDFIP2), a short half-life lysosomal membrane protein, negatively controls down-regulation of connexin43 (2010)
  • Author(s): C.Ohzono, S.Etoh, M.Matsumoto, K.I.Nakayama, Y.Hirota, Y.Tanaka, H.Fujita
  • Journal Title: Biol.Pharm.Bull. (Accepted)
  • Peer Reviewed
• [Journal Article] HIV-1 accessory protein Vpu internalizes cell-surface BST-2/tetherin through transmembrane interactions leading to lysosomes (2009)
  • Author(s): Y. Iwabu, H. Fujita, M. Kinomoto, K. Kaneko, Y. Ishizaka, Y. Tanaka, T. Sata, and K. Tokunaga.
  • Journal Title: J. Biol. Chem Volume: 284 Pages: 35060-35072
  • Peer Reviewed
• [Journal Article] HM1. 24 is internalized from lipid rafts by clathrin-mediated endocytosis through interaction with alpha-adaptin (2009)
  • Author(s): N. Masuyama, T. Kuronita, R. Tanaka, T. Muto, Y. Hirota, A. Takigawa, H. Fujita, Y. Aso, J. Amano and Y. Tanaka.
  • Journal Title: J. Biol. Chem Volume: 284 Pages: 15927-41
  • Peer Reviewed
• [Journal Article] Inulavosin, a melanogenesis inhibitor, leads a mistargeting of tyrosinase to lysosome and accelerates its degradation (2009)
  • Author(s): H. Fujita, T. Motokawa, T. Katagiri, S. Yokota, A. Yamamoto, M. Himeno and Y. Tanaka.
  • Journal Title: J. Investig. Dermatol Volume: 129 Pages: 1489-99
  • Peer Reviewed
• [Journal Article] Inulavosin, a melanogenesis inhibitor, leads a mistargeting of tyrosinase to lysosome and accelerates its degradation (2009)
  • Author(s): H.Fujita, T.Motokawa, T.Katagiri, S.Yokota, A.Yamamoto, M.Himeno, Y.Tanaka
  • Journal Title: J.Investig.Dermatol. 129 Pages: 1489-1499
  • Peer Reviewed
• [Journal Article] HM1.24 is internalized from lipid rafts by clathrin-mediated endocytosis through interaction with alpha-adaptin (2009)
  • Author(s): N.Masuyama, T.Kuronita, R.Tanaka, T.Muto, Y.Hirota, A.Takigawa, H.Fujita, Y.Aso, J.Amano, Y.Tanaka
  • Journal Title: J.Biol.Chem. 284 Pages: 15927-15941
  • Peer Reviewed
• [Journal Article] HIV-1 accessory protein Vpu internalizes cell-surface BST-2/tetherin through transmembrane interactions leading to lysosomes (2009)
  • Author(s): Y.Iwabu, H.Fujita, M.Kinomoto, K.Kaneko, Y.Ishizaka, Y.Tanaka, T.Sata, K.Tokunaga
  • Journal Title: J.Biol.Chem. 284 Pages: 35060-35072
  • Peer Reviewed
• [Journal Article] Inhibitory effects of 16-hydroxy-9-oxo-10E, 12E, 14E-octadecatrienoic acid (Corchorifatty acid B) isolated from Melissa officinalis Linne on melanogenesis
  • Author(s): H.Fujita, M.Hongo, M.Mochizuki, K.Yokoyama, Y.Tanaka
  • Journal Title: Experimental Dermatology Volume: (In press)
  • Peer Reviewed
• [Presentation] 膜結合型ユビキチンリガーゼMARCH8によるトランスフェリン受容体ダウンレギュレーションの分子機構 (2012)
  • Author(s): 藤田英明、岩部幸枝、佐多徹太郎、徳永研三、田中嘉孝
  • Organizer: 日本薬学会第132年会シンポジウム
  • Place of Presentation: 北海道大学(札幌)(招待講演)
  • Year and Date: 2012-03-29
• [Presentation] 膜結合型ユビキチンリガーゼMARCH8によるトランスフェリン受容体ダウンレギュレーションの分子機構 (2012)
  • Author(s): 藤田英明、岩部幸枝、佐多徹太郎、徳永研三、田中嘉孝
  • Organizer: 日本薬学会第132年会・シンポジウム「メタロミクス研究の新展開-金属元素の1細胞分析から疾患との関連まで-
  • Place of Presentation: 札幌
• [Presentation] 物誘発性リン脂質症の分子機構に関する研究 (2012)
  • Author(s): 廣田有子、藤本景子、栗原俊祐、阿佐絵里佳、池田一彦、佐野孝一、神吉将之、関二郎、藤田英明、田中嘉孝
  • Organizer: 第27回日本薬学会九州支部大会
  • Place of Presentation: 長崎大学
• [Presentation] Targeting of recycling endosomes to the cleavage furrow requires ubiquitylation of membrane proteins (2012)
  • Author(s): H. Fujita, Y. Iwabu, K. Tokunaga, T. Sata, K. Fujimoto, R. Tachiyama, D. Ishikawa, M. Matsumoto, K. I. Nakayama, and Y. Tanaka.
  • Organizer: AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY Special Symposium"BIOCHEMISTRY AND CELL BIOLOGY OF ESCRTS IN HEALTH AND DISEASE
  • Place of Presentation: Utah, USA
• [Presentation] Direct internalization of cell-surface BST-2/tetherin by HIV-1 Vpu (2012)
  • Author(s): Y. Iwabu, H. Fujita, Y. Tanaka, T. Sata, and K. Tokunaga.
  • Organizer: CRM 2010-Centennial Retrovirus Meeting
  • Place of Presentation: Institute of Molecular Genetics, Prague, Czech Republic
• [Presentation] 膜結合型ユビキチンリガーゼMARCH8によるトランスフェリン受容体のユビキチン化およびダウンレギュレーションの分子機構 (2011)
  • Author(s): 藤田英明、岩部幸枝、佐多徹太郎、徳永研三、田中嘉孝
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都国際会館(京都)
  • Year and Date: 2011-09-22
• [Presentation] Trans-Golgi network膜タンパク質TGN46の細胞内輸送および局在化の分子制御機構 (2011)
  • Author(s): 藤本景子、吉永奈央、平井祥一、藤田英明、廣田有子、田中嘉孝
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都国際会館(京都)
  • Year and Date: 2011-09-22
• [Presentation] ユビキチン化による金属輸送体の細胞内輸送制御 (2011)
  • Author(s): 藤田英明、立山諒、石川大輔、松本雅記、中山敬一、横田貞記、吉森保、姫野勝、田中嘉孝
  • Organizer: 日本薬学会第131年会・特別シンポジウム「トキシコメタロミクスの新機軸-元素分析・イメージングと金属輸送・創薬のイノベーション-」
  • Place of Presentation: 静岡(地震のため、本年会は参集しないが、成立したものとみなされる。)(招待講演)
  • Year and Date: 2011-03-30
• [Presentation] 膜結合型ユビキチンリガーゼMARCH8によるトランスフェリン受容体のユビキチン化およびダウンレギュレーションの分子機構 (2011)
  • Author(s): 藤田英明、岩部幸枝、佐多徹太郎、徳永研三、田中嘉孝
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
• [Presentation] Trans-Golgi network膜タンパク質TGN46の細胞内輸送および局在化の分子制御機構 (2011)
  • Author(s): 藤本景子、吉永奈央、平井祥一、藤田英明、廣田有子、田中嘉孝
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
• [Presentation] 「ユビキチン化による金属輸送体の細胞内輸送制御 (2011)
  • Author(s): 藤田英明、立山諒、石川大輔、松本雅記、中山敬一、横田貞記、吉森保、姫野勝、田中嘉孝
  • Organizer: 「ユビキチン化による金属輸送体」日本薬学会第131年会・特別シンポジウムE「トキシコメタロミクスの新機軸.元素分析・イメージングと金属輸送・創薬のイノベーション
• [Presentation] 鉄濃度依存的なトランスフェリン受容体のユビキチン化による代謝回転制御に関する研究 (2010)
  • Author(s): 藤田英明、立山諒、松本雅記、中山敬一、吉森保、姫野勝、横田貞記、田中嘉孝
  • Organizer: 第27回 日本薬学会九州支部大会
  • Place of Presentation: 長崎
  • Year and Date: 2010-12-12
• [Presentation] 物誘発性リン脂質症の分子機構に関する研究 (2010)
  • Author(s): 廣田有子、藤本景子、栗原俊祐、阿佐絵里佳、池田一彦、佐野孝一、神吉将之、関二郎、藤田英明、田中嘉孝
  • Organizer: 第27回 日本薬学会九州支部大会
  • Place of Presentation: 長崎
  • Year and Date: 2010-12-12
• [Presentation] Trans-Golgi network膜タンパク質TGN46の細胞内輸送および局在化の分子制御機構に関する研究 (2010)
  • Author(s): 藤本景子、吉永奈央、平井祥一、廣田有子、静川直子、藤田英明、田中嘉孝
  • Organizer: 第27回 日本薬学会九州支部大会
  • Place of Presentation: 長崎
  • Year and Date: 2010-12-11
• [Presentation] The endosomal vesicles carrying ubiquitylated cargos selectively localizes to the cleavage furrow during cytokinesis. (2010)
  • Author(s): H.Fujita, Y.Iwabu, K.Tokunaga, T.Sata, K.Fujimoto, R.Tachiyama, D.Ishikawa, M.Matsumoto, K.I.Nakayama, Y.Tanaka
  • Organizer: BMB2010(第83回日本生化学会大会/第33回日本分子生物学会年会)
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] BST-2/tetherinのdownregulationにおけるHIV-1 Vpuのcofactor要求性 (2010)
  • Author(s): 岩部幸枝, 藤田英明, 田中嘉孝, 佐多徹太郎, 徳永研三
  • Organizer: BMB2010(第83回日本生化学会大会/第33回日本分子生物学会年会)
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-07
• [Presentation] Targeting of recycling endosomes to the cleavage furrow requires ubiquitylation of membrane proteins. (2010)
  • Author(s): H.Fujita, Y.Iwabu, K.Tokunaga, T.Sata, K.Fujimoto, R.Tachiyama, D.Ishikawa, M.Matsumoto, K.I.Nakayama, Y.Tanaka
  • Organizer: AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY Special Symposium "BIOCHEMISTRY AND CELL BIOLOGY OF ESCRTS INHEALTH AND DISEASE"
  • Place of Presentation: Snowbird Ski and Summer Resort, Utah, USA
  • Year and Date: 2010-10-15
• [Presentation] Direct internalization of cell-surface BST-2/tetherin by HIV-1 Vpu (2010)
  • Author(s): Y.Iwabu, H.Fujita, Y.Tanaka, T.Sata, K.Tokunaga
  • Organizer: CRM 2010-Centennial Retrovirus Meeting
  • Place of Presentation: Institute of Molecular Genetics, Prague, Czech Republic
  • Year and Date: 2010-04-30
• [Presentation] 鉄濃度依存的なトランスフェリン受容体のユビキチン化による代謝回転制御に関する研究 (2010)
  • Author(s): 藤田英明、立山諒、松本雅記、中山敬一、吉森保、姫野勝、横田貞記、田中嘉孝
  • Organizer: 第27回日本薬学会九州支部大会
  • Place of Presentation: 長崎大学
• [Presentation] 「Trans-Golgi network膜タンパク質TGN46の細胞内輸送および局在化の分子制御機構に関する研究 (2010)
  • Author(s): 藤本景子、吉永奈央、平井祥一、廣田有子、静川直子、藤田英明、田中嘉孝
  • Organizer: 第27回日本薬学会九州支部大会
  • Place of Presentation: 長崎大学
• [Presentation] The endosomal vesicles carrying ubiquitylated cargos selectively localizes to the cleavage furrow during cytokinesis (2010)
  • Author(s): H. Fujita, Y. Iwabu, K. Tokunaga, T. Sata, K. Fujimoto, R. Tachiyama, D. Ishikawa, M. Matsumoto, K. I. Nakayama, and Y. Tanaka.
  • Organizer: 第83回日本生化学会大会/第33回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] BST-2/tetherinのdownregulationにおけるHIV-1 Vpuのcofactor要求性 (2010)
  • Author(s): 岩部幸枝,藤田英明,田中嘉孝,佐多徹太郎,徳永研三
  • Organizer: 第83回日本生化学会大会/第33回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] HIV-1 Vpu internalizes cell-surface BST-2/tetherin and leads it to lysosomes (2010)
  • Author(s): Y. Iwabu, H. Fujita, M. Kinomoto, K. Kaneko, Y. Ishizaka, Y. Tanaka, T. Sata and K. Tokunaga
  • Organizer: The 17^<th> Conference on Retroviruses and Opportunistic Infections
  • Place of Presentation: Sam Francisco, CA, USA
• [Presentation] HIV-1 Vpu internalizes cell-surface BST-2/tetherin and leads it to lysosomes (2010)
  • Author(s): Y.Iwabu, H.Fujita, M.Kinomoto, K.Kaneko, Y.Ishizaka, Y.Tanaka, T.Sata, K.Tokunaga
  • Organizer: The 17th Conference on Retroviruses and Opportunistic Infections (CROI 2010)
  • Place of Presentation: Sam Francisco, CA, USA
• [Presentation] Inhibitory effect of active compound isolated from Melissa officinalis Linne(Labiatae) on melanogenesis and phagocytosis (2009)
  • Author(s): M. Hongo, H. Fujita, M. Mochizuki, T. Kato, K. Yokoyama, Y. Tanaka.
  • Organizer: 34^<th> Annual Meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: Workshop, Fuluoka
• [Presentation] BST-2/TetherinとHIV-1 Vpuの相互作用における結合領域の同定 (2009)
  • Author(s): 岩部幸枝、藤田英明、石坂幸人、田中嘉孝、佐多徹太郎、徳永研三
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] HIV-1 VpuとBST-2/TetherinのTransmembrane領域間における相互作用 (2009)
  • Author(s): 岩部幸枝、藤田英明、石坂幸人、田中嘉孝、佐多徹太郎、徳永研三
  • Organizer: 第57回日本ウイルス学会
  • Place of Presentation: 東京
• [Presentation] HIV-1 Vpuによるウイルス放出抑制因子BST-2/Tetherinの細胞内分解経路の解明 (2009)
  • Author(s): 岩部幸枝、藤田英明、石坂幸人、田中嘉孝、佐多徹太郎、徳永研三
  • Organizer: 第57回日本ウイルス学会
  • Place of Presentation: 東京
• [Presentation] 過剰鉄によるユビキチン化がトランスフェリン受容体のリソソームでのダウンレギュレーションを引き起こす (2009)
  • Author(s): 藤田英明、立山諒、石川大輔、松本雅記、中山敬一、横田貞記、吉森保、姫野勝、田中嘉孝
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
• [Presentation] HIV-1 VpuとBST-2/Tetherin の Transmembrane 領域間における相互作用 (2009)
  • Author(s): 岩部幸枝, 藤田英明, 石坂幸人, 田中嘉孝, 佐多徹太郎, 徳永研三
  • Organizer: 第57回日本ウイルス学会
  • Place of Presentation: 東京
• [Presentation] HIV-1 Vpu によるウイルス放出抑制因子BST-2/Tetherin の細胞内分解経路の解明 (2009)
  • Author(s): 岩部幸枝, 藤田英明, 石坂幸人, 田中嘉孝, 佐多徹太郎, 徳永研三
  • Organizer: 第57回日本ウイルス学会
  • Place of Presentation: 東京
• [Presentation] BST-2/Tetherin とHIV-1 Vpu の相互作用における結合領域の同定 (2009)
  • Author(s): 岩部幸枝, 藤田英明, 石坂幸人, 田中嘉孝, 佐多徹太郎, 徳永研三
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜