Relationship between inflammation and novel NF-κB activation pathway which is regulated by ubiquitin system

• Project/Area Number: 20390097
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Osaka University
• Principal Investigator: TOKUNAGA Fuminori Osaka University, 医学系研究科, 准教授 (00212069)
• Co-Investigator(Kenkyū-buntansha): IWAI Kazuhiro 大阪大学, 大学院・生命機能研究科, 教授 (60252459)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥19,890,000 (Direct Cost: ¥15,300,000、Indirect Cost: ¥4,590,000); Fiscal Year 2010: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2009: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2008: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
• Keywords: 分子腫瘍学 / 蛋白質 / 酵素 / 細胞・組織 / 炎症 / ユビキチン

Research Abstract

We identified LUBAC ubiquitin ligase, which composed of SHARPIN, HOIL-1L, and HOIP, forms a novel type of linear polyubiquitin chain. LUBAC regulates NF-κB system, a critical transcription factor for inflammation and immune regulation. Furthermore, we revealed that cpdm mice, which lack Sharpen by a spontaneous mutation, induce dermatitis by the reduction of LUBAC and NF-κB activity. These results indicate that linear polyubiquitination is an indispensable post-transcription modification for NF-κB activation.

Research Products

• [Journal Article] SHARPIN is a component of the NF-kB activating linear ubiquitin assembly complex. (2011)
  • Author(s): Tokunaga F., Nakagawa T., Nakahara M., Saeki Y., Taniguchi M., S Sakata S.-i., Tanaka K., Nakano H., Iwai K.
  • Journal Title: Nature 471 Pages: 633-636
  • Peer Reviewed
• [Journal Article] SHARPIN forms a linear ubiquitin ligase complex regulating NF-κB activity and apoptosis. (2011)
  • Author(s): Ikeda F., Deribe Y.L, Skanland S.S., Stieglitz B., Grabbe C., van WijK S., Franz-Wachtel M., Goswami P., Nagy V., Terzic J., Tokunaga F., Androulidaki A., Nakagawa T., Pasparakis M., Iwai K., Sundberg J.P., Schaefer L., Macek B., Rittinger K., Dikic, I.
  • Journal Title: Nature 471 Pages: 637-641
  • Peer Reviewed
• [Journal Article] Linear ubiquitin assembly complex negatively regulates RIG-I- and TRIM25-mediated type I interferon induction. (2011)
  • Author(s): Inn K.S., Gack M.U., Tokunaga F., Shi M., Wong L.Y., Iwai K., Jung J.U.
  • Journal Title: Mol Cell 41 Pages: 354-365
  • Peer Reviewed
• [Journal Article] Sharpin is a component of the NF-κB activating linear ubiquitin assembly complex. (2011)
  • Author(s): Fuminori Tokunaga, et al.
  • Journal Title: Nature Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] SHARPIN forms a linear ubiquitin ligase complex regulating NF-κB activity and apoptosis. (2011)
  • Author(s): Fumiyo Ikeda, et al.
  • Journal Title: Nature Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Linear ubiquitin assembly complex negatively regulates RIG-I-and TRIM25-mediated type I interferon induction. (2011)
  • Author(s): Kyung-Soo Inn, et al.
  • Journal Title: Mol.Cell Volume: 41 Pages: 354-365
  • Peer Reviewed
• [Journal Article] ユビキチン修飾系によるNF-κBグナル伝達制御:新規直鎖状ポリユビキチン鎖形成を介するNF-κB制御機構の発見 (2010)
  • Author(s): 徳永文稔、岩井一宏
  • Journal Title: 細胞工学 29 Pages: 1224-1230
• [Journal Article] ユビキチンープロテアソーム系の多彩な生理機能と疾患への関与 (2010)
  • Author(s): 徳永文稔
  • Journal Title: BIO Clinica 25 Pages: 1092-1097
• [Journal Article] Crystallization and prelimiary X-ray characterization of the Skp1-Fbg3 complex. (2010)
  • Author(s): Kumanomidou T., Nakagawa T., Mizushima T., Suzoki A., Tokunaga F., Iwai K., Yoshida Y., Tanaka K., Yamane T.
  • Journal Title: Acta Crystallogr.Sect.F Struct.Biol.Cryst.Commun 66 Pages: 95-98
  • Peer Reviewed
• [Journal Article] Crystallization and preliminary X-ray characterization of the Skpl-Fbg3 complex (2010)
  • Author(s): Kumanomidou T., et al.
  • Journal Title: Acta Crystallogr Sect F Struct Biol Cryst Commun. 66 Pages: 95-98
  • Peer Reviewed
• [Journal Article] Linear polyubiquitination : a new regulator of NF-kB activation. (2009)
  • Author(s): 岩井一宏, 徳永文稔
  • Journal Title: EMBO Rep. 10 Pages: 706-713
  • Peer Reviewed
• [Journal Article] アレルギーやガンに関わるNF-κBの新しい活性化機構の発見:新規ユビキチン修飾 (2009)
  • Author(s): 岩井一宏、坂田真一、中川朋子、徳永文稔
  • Journal Title: 直鎖状ポリユビキチン化によるNF-κB活性化.化学と生物 47 Pages: 602-604
• [Journal Article] NEMOの直鎖状ポリユビキチン化修飾によるNF-κB活性化 (2009)
  • Author(s): 徳永文稔、岩井一宏
  • Journal Title: 蛋白質核酸酵素 54 Pages: 635-642
• [Journal Article] Involvement of linear polyubiquitylation of NEMO in NF-κB activation. (2009)
  • Author(s): Tokunaga F., Sakata S.-i., Saeki Y., Satomi Y., Kirisako T., Kamei K., Nakagawa T., Kato M., Murata S., Yamaoka S., Yamamoto M., Akira S., Takao T., Tanaka K., Iwai K.
  • Journal Title: Nature Cell Biol. 11 Pages: 123-132
  • Peer Reviewed
• [Journal Article] Linear polyubiquitination : a new regulator of NF-κB activation (2009)
  • Author(s): Iwai K., Tokunaga F.
  • Journal Title: EMBO Rep. 10 Pages: 706-713
  • Peer Reviewed
• [Journal Article] Involvement of linear polyubiquitylation of NEMO in NF-kB activation (2009)
  • Author(s): Tokunaga, F., et al.
  • Journal Title: Nature Cell Biology 11 Pages: 123-132
  • Peer Reviewed
• [Journal Article] The COP9/signalosome increases the efficiency of von Hippel-Linubiquitin ligase-mediated hypoxia-inducible factor-alpha ubiquitination. (2008)
  • Author(s): Miyauchi Y., Kato M., Tokunaga F., Iwai K.
  • Journal Title: J.Biol.Chem. 283 Pages: 1662-16631
  • Peer Reviewed
• [Journal Article] gp78 cooperates with RMA1 in ER-associadegradation of CFTRDF508. (2008)
  • Author(s): Morito D., Hirao K., Oda Y., Hosokawa N., Tokunaga F., Cyr D.M., Tanaka K., Iwai K., Nagata K.
  • Journal Title: Mol.Biol.Cell 19 Pages: 1328-1336
  • Peer Reviewed
• [Journal Article] The COP9/signalosomeubiquitin ligase-mediatedncreases the efficiency of von Hhypoxia-inducible factor-α ubiquppel-Lindau proteintination (2008)
  • Author(s): Miyauchi, Y., et al.
  • Journal Title: J. Biol. Chem. . 283 Pages: 16622-16631
  • Peer Reviewed
• [Journal Article] Gp78 cooperates with RMAl in endoplasmic reticulum-associateddegradation of CFTRΔF508. (2008)
  • Author(s): Morito, D., et al.
  • Journal Title: Mol. Biol. Cell 19 Pages: 1328-1336
  • Peer Reviewed
• [Presentation] 新規直鎖状ポリユビキチン鎖形成を介したNF-κBシグナル制御(シンポジウム) (2011)
  • Author(s): 徳永文稔
  • Organizer: 新学術領域研究「修飾シグナル病」第1回公開シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2011-01-29
• [Presentation] Linear polyubiquitination : A new regulator of NF-κB activation(Invited Lecture). (2010)
  • Author(s): 徳永文稔
  • Organizer: Pacifichem
  • Place of Presentation: Honolulu, U.S.A
  • Year and Date: 2010-12-08
• [Presentation] 新規直鎖状ポリユビキチン化によるNF-κB活性化制御と疾患(ワークショップ) (2010)
  • Author(s): 徳永文稔、岩井一宏
  • Organizer: VMB2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] 直鎖状ポリユビキチン化によるNF-κB活性化制御と疾患 (2010)
  • Author(s): 徳永文稔
  • Organizer: BMB2010(ワークショップ)
  • Place of Presentation: 神戸ポートピアホテル(招待講演)
  • Year and Date: 2010-12-08
• [Presentation] 直鎖状ポリユビキチン鎖生成ユビキチンリガーゼ(LUBAC)の新規サブユニットの同定 (2010)
  • Author(s): 徳永文稔、岩井一宏
  • Organizer: 第2回シグナルネットワーク研究会
  • Place of Presentation: 大阪
  • Year and Date: 2010-05-14
• [Presentation] 直鎖状ポリユビキチン化:NF-κB活性化を導く新たなポリユビキチン鎖(ワークショップ) (2009)
  • Author(s): 徳永文稔、中川朋子、坂田真一、岩井一宏
  • Organizer: 第32回日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-10
• [Presentation] 直鎖状ポリユビキチン化:NF-κB活性化を導く新たなポリユビキチン鎖 (2009)
  • Author(s): 徳永文稔
  • 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: 2009-12-10
• [Presentation] 新規直鎖状ポリユビキチン鎖生成を介するNF-κB経路の活性化(シンポジウム) (2009)
  • Author(s): 徳永文稔
  • Organizer: 第19回WSフォーラム-タンパク質・ペプチド研究の現状と展望-
  • Place of Presentation: 福岡
  • Year and Date: 2009-11-27
• [Presentation] NEM2分子以上の直鎖状ポリユビキチン化はNF-κB活性化を導く (2009)
  • Author(s): 徳永文稔、亀井希代子、岩井一宏
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-23
• [Presentation] NEMOの2分子以上の直鎖状ポリユビキチン化はNF-KB活性化を導く (2009)
  • Author(s): 徳永文稔
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2009-10-23
• [Presentation] Linear ubiquitination : a novel type of polyubiquitin chain for NF-κB activatio(Invited Lecture). (2009)
  • Author(s): 徳永文稔
  • Organizer: 第7回血液血管オルビス
  • Place of Presentation: 東京
  • Year and Date: 2009-08-23
• [Presentation] 直鎖状ポリユビキチン化:NF-κB活性化に必須な新たなユビキチン修飾系(シンポジウム) (2009)
  • Author(s): 徳永文稔、岩井一宏
  • Organizer: 第1回シグナルネットワーク研究会
  • Place of Presentation: 東京
  • Year and Date: 2009-05-29
• [Presentation] LUBACユビキチンリガーゼによるNEMOの直鎖状ポリユビキチン化修飾とNF-κB活性化の分子機構 (2008)
  • Author(s): 徳永文稔、坂田真一、佐伯泰、亀井希代子、中川朋子、山岡昇司、山本雅裕、審良静男、高尾敏文、田中啓二、岩井一宏
  • Organizer: BMB2008
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] LUBACユビキチンリガーゼによるNEMOの直鎖状ポリユビキチン化修飾とNF-kB活性化の分子機構 (2008)
  • Author(s): 徳永文稔
  • Organizer: 第31回日本分子生物学会、第81回日本生化学会合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-11
• [Book] アグリソーム他6項目,キーワード:蛋白質の一生(遠藤斗志也, 小椋光, 永田和宏, 森和俊, 田口英樹,吉田賢右(編)) (2008)
  • Author(s): 徳永文稔
  • Publisher: 共立出版
• [Remarks] ホームページ等
  • URL: http://www.cellbio.med.osaka-u.ac.jp/
• [Remarks] 大阪大学大学院医学系研究科医化学教室
  • URL: http://www.cellbio.med.osaka-u.ac.jp/
• [Remarks] 新学術領域研究「修飾シグナル病」HP
  • URL: http://shushoku-signal.com/
• [Remarks] 大阪大学大学院医学系研究科主要成果
  • URL: http://www.med.osaka-u.ac.jp/jp/seika/index.html
• [Remarks] 大阪大学大学院生命機能研究科最近の研究から
  • URL: http://www.fbs.osaka-u.ac.jp/pr/jp/saikin/iwail.html
• [Remarks] 研究室Webページ
  • URL: http://www.cellbio.med.osaka-u.ac.jp/
• [Remarks] 大阪大学大学院医学系研究科主要成果:
  • URL: http://www.med.osaka-u.ac.jp/jp/seika/index.html
• [Remarks] 大阪大学大学院生命機能研究科研究成果:
  • URL: http://www.fbs.osaka-u.ac.jp/publications/iwai2009/index.html
• [Remarks] 研究室Webページ:
  • URL: http://www.cellbio.med.osaka-u.ac.jp/