ユビキチンネオバイオロジー：拡大するタンパク質制御システム

• Project Area: New aspect of the ubiquitin system : its enormous roles in protein regulation
• Project/Area Number: 24112001
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Research Institution: Kyoto University
• Principal Investigator: 岩井 一宏 京都大学, 医学研究科, 教授 (60252459)
• Co-Investigator(Kenkyū-buntansha): 駒田 雅之 東京工業大学, 大学院生命理工学研究科, 教授 (10225568) ; 嘉村 巧 名古屋大学, 理学研究科, 教授 (40333455) ; 佐伯 泰 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 副参事研究員 (80462779)
• Project Fiscal Year: 2012-06-28 – 2017-03-31
• Project Status: Granted(Fiscal Year 2016)
• Budget Amount: ¥47,970,000 (Direct Cost : ¥36,900,000、Indirect Cost : ¥11,070,000); Fiscal Year 2016 : ¥9,360,000 (Direct Cost : ¥7,200,000、Indirect Cost : ¥2,160,000); Fiscal Year 2015 : ¥9,360,000 (Direct Cost : ¥7,200,000、Indirect Cost : ¥2,160,000); Fiscal Year 2014 : ¥13,130,000 (Direct Cost : ¥10,100,000、Indirect Cost : ¥3,030,000); Fiscal Year 2013 : ¥9,360,000 (Direct Cost : ¥7,200,000、Indirect Cost : ¥2,160,000); Fiscal Year 2012 : ¥6,760,000 (Direct Cost : ¥5,200,000、Indirect Cost : ¥1,560,000)
• Keywords: 生体分子 / ユビキチン / タンパク質 / 翻訳後修飾 / 領域内研究者交流 / 情報交換 / 研究技法共有

Outline of Annual Research Achievements

タンパク質性の翻訳後修飾因子であるユビキチンは、発見された経緯からタンパク質分解と関連して研究が発展した。しかし近年、ユビキチン修飾は分解以外の様式でもタンパク質の機能を制御して、広汎な生命現象に関与していることが明確となりつつある。ユビキチンは「ユビキチンコード」と定義できるほど多様な様式で標的タンパク質に付加されてそれらの機能を制御しており、生命科学におけるユビキチン修飾系の重要性は益々拡大すると想定されている。
今後の我が国のユビキチン研究の発展に不可欠である最先端の解析技術の開発と、ユビキチンコードによる新たな生命機能制御メカニズムの解析を進めるために、領域の計画研究の研究代表者と分担研究者が本研究課題に分担研究者あるいは連携研究者として加わり役割を分担して領域を運営している。
平成26年度には25年度に領域内で新たに樹立された研究試料、情報等を記載するなどの充実を研究情報交換窓口に進めた。また、11月に海外の著名研究者を招へいして国際シンポジウムを開催するとともに、国際シンポジウムに参加した外国人研究者をセッションチェアーになっていただき、領域の若手研究者が英語で口頭、ポスター発表を行う若手シンポジウムを共催した。若手シンポジウムは外国人研究者からも非常に好評であった。

Current Status of Research Progress

Research has progressed on the whole more than it was originally planned.

Reason

領域の中間評価はA判定であり、順調に推移していると評価された。

Research Output

• [Journal Article] The unexpected role of polyubiquitin chains in the formation of fibrillar aggregates. (2015)
  • Author(s): Morimoto, D., Walinda, E., Fukada, H., Sou, Y. S., Kageyama, S., Hoshino, M., Fujii, T., Tsuchiya, H., Saeki, Y., Arita, K., Ariyoshi, M., Tochio, H., Iwai, K., Namba, K., Komatsu, M., Tanaka, K., Shirakawa, M.
  • Journal Title: Nat. Commun Volume : 6 Pages : 6116
  • DOI: 10.1038/ncomms7116
• [Journal Article] Gliotoxin suppresses NF-κB activation by selectively inhibiting linear ubiquitin chain assembly complex (LUBAC). (2015)
  • Author(s): Sakamoto, H., Egashira, S., Saito, N., Kirisako, T., Miller, S., Sasaki, Y., Matsumoto, T., Shimonishi, M., Komatsu, T., Terai, T., Ueno, T., Hanaoka, K., Kojima, H., Okabe, T., Wakatsuki, S., Iwai, K., (corresponding author) and Nagano, T
  • Journal Title: ACS Chem. Biol. Volume : 10 Pages : 675-681
  • DOI: 10.1021/cb500653y
• [Journal Article] Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus infection. (2015)
  • Author(s): MacDuff, D. A., Reese, T. A,, Kimmey, J. M., Weiss, L. A., Song, C., Zhang, X., Kambal, A., Duan, E., Carrero, J. A., Boisson, B., Laplantine, E., Israel, A., Picard, C., Colonna, M., Edelson, B. T., Sibley, L. D., Stallings, C. L., Casanova, J. L., Iwai, K., Virgin, H. W.
  • Journal Title: eLife Volume : 4 Pages : e04494
  • DOI: 10.7554/eLife.04494
• [Journal Article] Suppression of LUBAC-mediated linear ubiquitination by a specific interaction between LUBAC and the deubiquitinases CYLD and OTULIN. (2014)
  • Author(s): Takiuchi, T., Nakagawa, T., Tamiya, H., Fujita, H., Sasaki, Y., Saeki, Y., Takeda, H., Sawasaki, T., Buchberger, A., Kimura, T., and Iwai. K.
  • Journal Title: Genes Cells. Volume : 19 Pages : 254-272
  • DOI: 10.1111/gtc.12128
• [Journal Article] Mechanism underlying IKK activation mediated by the linear ubiquitin chain assembly complex (LUBAC). (2014)
  • Author(s): Fujita, H., Rahighi, S., Akita, M., Kato, R., Sasaki, Y., Wakatsuki, S., and Iwai, K.
  • Journal Title: Mol. Cell. Biol. Volume : 34 Pages : 1322-1335
  • DOI: 10.1128/MCB.01538-13
• [Journal Article] Essential role of the linear ubiquitin chain assembly complex in lymphoma revealed by rare germline polymorphisms. (2014)
  • Author(s): Yang, Y., Schmitz, R., et al.
  • Journal Title: Cancer Discov. Volume : 4 Pages : 480-493
  • DOI: 10.1158/2159-8290. CD-13-0915
• [Journal Article] IFN-γ or IFN-α ameliorates chronic proliferative dermatitis by inducing expression of linear ubiquitin chain assembly complex. (2014)
  • Author(s): Tamiya H, Terao M, Takiuchi T, Nakahara M, Sasaki Y, Katayama I, Yoshikawa H, and Iwai K.
  • Journal Title: J. Immunol. Volume : 192 Pages : 3793-3804
  • DOI: 10.4049/jimmunol.1302308
• [Journal Article] The linear ubiquitin assembly complex (LUBAC) is essential for NLRP3 inflammasome activation. (2014)
  • Author(s): Rodgers, M. A., Bowman, J., Fujita, H., Orazio, N., Shi, M., Liang, Q., Amatya, R., Kelly, T. J., Iwai, K., Ting, J., and Jung, J. U.
  • Journal Title: J. Exp. Med. Volume : 211 Pages : 1333-1347
  • DOI: 10.1084/jem.20132486
• [Journal Article] HOIL-1L Functions as the PKCζ Ubiquitin Ligase to Promote Lung Tumor Growth. (2014)
  • Author(s): Queisser, M. A., Dada, L. A., Deiss-Yehiely, N., Angulo, M., Zhou, G., Kouri, F. M., Knab, L. M., Liu, J., Stegh, A. H., DeCamp, M. M., Budinger, G. R., Chandel, N. S., Ciechanover, A., Iwai, K., and Sznajder, J. I.
  • Journal Title: Am. J. Respir. Crit. Care Med. Volume : 190 Pages : 688-698
  • DOI: 10.1164/rccm.201403-0463OC
• [Journal Article] Linear ubiquitin chains: NF-κB signalling, cell death, and beyond. (2014)
  • Author(s): Iwai, K., Fujita, H., and Sasaki, Y.
  • Journal Title: Nature Rev. Mol. Cell Biol. Volume : 15 Pages : 503-508
  • DOI: 10.1038/nrm3836
• [Journal Article] Ubiquitin chain elongation: An intriguing strategy. (2014)
  • Author(s): Iwai, K. and Tanaka, K.
  • Journal Title: Molecular Cell Volume : 56 Pages : 189–191
  • DOI: 10.1016/j.molcel.2014.10.009
• [Journal Article] Defective immune responses in mice lacking LUBAC-mediated linear ubiquitination in B cells. (2013)
  • Author(s): Sasaki, Y., Sano, S., Nakahara, M., Murata, S., Kometani, K., Aiba, Y., Sakamoto, S., Watanabe, Y., Tanaka, K., Kurosaki, K. and Iwai, K.
  • Journal Title: EMBO J. Volume : 32 Pages : 2463-2476
  • DOI: 10.1038/emboj.2013.184
• [Journal Article] Recruitment of the autophagic machinery to endosomes during infection is mediated by ubiquitin. (2013)
  • Author(s): Fujita, N., Morita, E., Itoh, T., Tanaka, A., Nakaoka, M., Osada, Y., Umemoto, T., Saitoh, T., Nakatogawa, H., Kobayashi, S., Haraguchi, T., Guan, J.L., Iwai, K., Tokunaga, F., Saito, K., Ishibashi, K., Akira, S., Fukuda, M., Noda, T., and Yoshimori, T.
  • Journal Title: J. Cell Biol. Volume : 203 Pages : 115-128
  • DOI: 10.1083/jcb.201304188
• [Journal Article] Two coordinated mechanisms underlie TNFα-induced immediate and delayed IKK activation. (2013)
  • Author(s): Blackwell, K., Zhang, L., Workman, L.M., Ting, A.T., Iwai, K., Habelhah, H.
  • Journal Title: Mol. Cell. Biol. Volume : 33 Pages : 1901-1915
  • DOI: 10.1128/MCB.01416-12
• [Journal Article] IOP1 protein is an external component of the human cytosolic iron-sulfur cluster assembly (CIA) machinery and functions in the MMS19 protein-dependent CIA pathway. (2013)
  • Author(s): Seki, M., Takeda, Y., Iwai, K., and Tanaka, K.
  • Journal Title: J. Biol. Chem. Volume : 288 Pages : 16680-16689
  • DOI: 10.1074/jbc.M112.416602.
• [Presentation] Phenotypical difference between mice lacking subunits of LUBAC ubiquitin ligase. (2014)
  • Author(s): Iwai, K.
  • Organizer: 1st International Symposium for New Aspects of the Ubiquitin Research
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2014-11-10
• [Presentation] Mechanism underlying linear ubiquitin-mediated NF-κB activation. (2014)
  • Author(s): Iwai, K.
  • Organizer: Benzon Symposium Nuclear regulation by ubiquitin
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2014-08-18 – 2014-08-21
• [Presentation] Linear ubiquitination : a new regulator of NF-κB and cell death signaling. (2014)
  • Author(s): Iwai, K.
  • Organizer: 2014 International Conference on Protein Metabolism & Diseases
  • Place of Presentation: Yangyang, Korea
  • Year and Date: 2014-07-09 – 2014-07-11
• [Presentation] Molecular mechanism and regulation of linear chain-mediated NF-κB activation. (2014)
  • Author(s): Fujita, H., Takiuchi, T., and Iwai, K.
  • Organizer: Cold Spring Harbor Asia Conference “ Protein Modifications & Homeostasis”
  • Place of Presentation: Suzhou, China
  • Year and Date: 2014-06-16 – 2014-06-20
• [Presentation] Linear Polyubiquitination: a Crucial Regulator of NF-κB Activation. (2014)
  • Author(s): Iwai, K.
  • Organizer: THE UEHARA MEMORIAL FOUNDATION SYMPOSIUM 2014, Innovative Medicine : Basic Research and Development.
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2014-06-14 – 2014-06-17
• [Presentation] Differential requirement of LUBAC-mediated linear polyubiquitination in CD40- or BCR-mediated canonical NF-κB activation in B cells (2013)
  • Author(s): Sasaki, Y., Fujita, H., and Iwai, K.
  • Organizer: The EMBO Conference “Ubiquitin and Ubiquitin-like Proteins: From structure to function”
  • Place of Presentation: Riva del Garda, Italy
  • Year and Date: 2013-10-01 – 2013-10-05
• [Presentation] Linear polyubiquitination: a new regulator of NF-κB activation. (2013)
  • Author(s): Iwai, K.
  • Organizer: The 35th Naito Conference “The Ubiquitin-Proteasome System: From Basic Mechanisms to Pathophysiological Roles”
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 2013-07-09 – 2013-07-12
• [Presentation] Linear polyubiquitination: a new regulator of NF-κB activation. (2013)
  • Author(s): Iwai, K.
  • Organizer: The 38th FEBS congress symposium “Regulation of biological processes by ubiquitin and ubiquitin-like proteins in health and disease: proteolysis, autophagy and apoptosis”
  • Place of Presentation: St. Petersburg, Russia
  • Year and Date: 2013-07-06 – 2013-07-12
• [Remarks] 新学術領域研究 ユビキチンネオバイオロジー：拡大するタンパク質制御システム
  • URL: http://ubiquitin.jp/
• [Remarks] 新学術領域研究 ユビキチンネオバイオロジー：拡大するタンパク質制御システム
  • URL: http://ubiquitin.jp/