Clarification of molecular mechanisms how PDLIM2, a nuclear ubiquitin E3 ligase, regulates inflammatory responses

• Project/Area Number: 20590499
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: TANAKA Takashi The Institute of Physical and Chemical Research, 炎症制御研究ユニット, ユニットリーダー (00415225)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 炎症反応 / PDLIM2 / NF-κB / HSP70 / 創傷治癒 / Smad2 / 3 / 炎症性肉芽腫 / STAT3 / 免疫学 / シグナル伝達 / アレルギー・ぜんそく / ユビキチンリガーゼ

Research Abstract

PDLIM2 negatively regulates inflammatory responses by promoting polyubiquitination and degradation of NF-κB, an essential transcription factor for the inflammation. In this study, we demonstrate that HSP70, a heat shock protein, is essential for PDLIM2-mediated degradation of NF-κB. Moreover, PDLIM2 deficient mice reveal enhanced inflammation and wound healing, which suggests that PDLIM2 negatively regulates both inflammatory and tissue repair responses and prevent the development of chronic inflammatory diseases.

Research Products

• [Journal Article] Conservation of a chemokine system, XCR1 and its ligand, XCL1, between human and mice. (2010)
  • Author(s): Yamazaki C., Miyamoto R., Hoshino K., Fukuda Y., Sasaki I., Saito M., Ishiguchi H. Yano T., Sugiyama T., Hemmi H., Tanaka T., Hamada E., Hirashima T., Amakawa R., Fukuhara S., Nomura S., Ito T., Kaisho T.
  • Journal Title: Biochem.Biophys.Res.Commun. 397 Pages: 756-761
  • Peer Reviewed
• [Journal Article] Ablation of C/EBPβ alleviates ER stress and pancreatic b cell failure through the GRP78 chaperone in mice. (2010)
  • Author(s): Matsuda T, Kido Y, Asahara S, Kaisho T, Tanaka T, Hashimoto N, Shigeyama Y, Takeda A, Inoue T, Shibutani Y, Koyanagi M, Hosooka T, Matsumoto M, Inoue H, Uchida T, Koike M, Uchiyama Y, Akira S, Kasuga M
  • Journal Title: J.Clin.Invest. 120 Pages: 115-126
  • Peer Reviewed
• [Journal Article] Conservation of a chemokine system, XCR1 and its ligand, XCL1, between human and mice. (2010)
  • Author(s): Chihiro Yamazaki
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 397 Pages: 756-761
  • Peer Reviewed
• [Journal Article] Ablation of C/EBP β alleviates ER stress and pancreatic β cell failure through the GRP78 chaperone in mice. (2010)
  • Author(s): Tomokazu Matsuda
  • Journal Title: J.Clin.Invest Volume: 120 Pages: 115-126
  • Peer Reviewed
• [Journal Article] PDLIM2 suppresses HTLV-I Tax-mediated tumorigenesis by targeting Tax into the nuclear matrix for proteasomal degradation. (2009)
  • Author(s): Yan P., Fu J., Qu Z., Li S., Tanaka T., Grusby M.J., Xiao G.
  • Journal Title: Blood 113 Pages: 4370-4380
  • Peer Reviewed
• [Journal Article] PDLIM2 suppresses HTLV-I Tax-mediated tumorgenesis by targeting Tax into the nuclear matrix for proteasomal degradation. (2009)
  • Author(s): Pengrong Yan
  • Journal Title: Blood Volume: 113 Pages: 4370-4380
  • Peer Reviewed
• [Journal Article] PDLIM2 suppresses HTLV-I Tax-mediated tumorgenesis by targeting Tax into the nuclear matrix for proteasomal degradation (2009)
  • Author(s): Pengrong Yan
  • Journal Title: Blood (印刷中)
  • Peer Reviewed
• [Journal Article] Turning NF-κB and IRFs on and off in DCs. (2008)
  • Author(s): Kaisho T., Tanaka T.
  • Journal Title: Trends Immunol. 29 Pages: 329-336
  • Peer Reviewed
• [Journal Article] Turning NF-κB and IRFs on and off in DCs (2008)
  • Author(s): Tsuneyasu Kaisho
  • Journal Title: Trends in Immunology 29 Pages: 329-336
  • Peer Reviewed
• [Presentation] HSP70 terminates NF-κB activation by facilitating degradation of the p65 subunit. (2011)
  • Author(s): 田中貴志
  • Organizer: 新学術領域研究「自然炎症」第1回若手ワークショップ
  • Place of Presentation: 蔵王、山形
  • Year and Date: 2011-01-26
• [Presentation] HSP70 terminates NF-κB activation by facilitating degradation of the p65 subunit (2011)
  • Author(s): 田中貴志
  • Organizer: 新学術領域研究「自然炎症」第1回若手ワークショップ
  • Place of Presentation: 蔵王、山形
  • Year and Date: 2011-01-26
• [Presentation] PDLIM2, a nuclear ubiquitin E3 ligase, negatively regulates inflammatory responses. (2010)
  • Author(s): 田中貴志
  • Organizer: INSERM/Pasteur-RIKEN Joint Workshop "Frontier in Immunology-From basic to clinics".
  • Place of Presentation: 横浜
  • Year and Date: 2010-08-31
• [Presentation] PDLIM2, a nuclear ubiquitin E3 ligase, negatively regulates inflammatory responses. (2010)
  • Author(s): Takashi Tanaka
  • Organizer: INSERM/Pasteur-RIKEN Joint Workshop "Frontier in Immunology-From basic to clinics"
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2010-08-31
• [Presentation] PDLIM2 regulates Th17-mediated responses through degradation of STAT3 transcription factor. (2010)
  • Author(s): 田中貴志
  • Organizer: The 14^<th> International Congress of Immunology.
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-23
• [Presentation] PDLIM2 regulates Th17-mediated responses through degradation of STAT3 transcription factor. (2010)
  • Author(s): Takashi Tanaka
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-08-23
• [Presentation] PDLIM2はTh17細胞分化を負に制御する (2009)
  • Author(s): 田中貴志、改正恒康
  • Organizer: 日本免疫学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-02
• [Presentation] PDHM2はTh17細胞分化を負に制御する (2009)
  • Author(s): 田中貴志
  • Organizer: 第39回日本免疫学会総会
  • Place of Presentation: (大阪国際会議場)大阪
  • Year and Date: 2009-12-02
• [Presentation] PDLIM2, a nuclear ubiquitin E3 ligase negatively regulates inflammatory responses. (2009)
  • Author(s): 田中貴志
  • Organizer: The 2009 fall conference of the Korean association of immunologists.
  • Place of Presentation: Seuol, Korea
  • Year and Date: 2009-11-10
• [Presentation] PDLIM2, a nuclear ubiquitin E3 ligase negatively regulates inflammatory responses. (2009)
  • Author(s): Takashi Tanaka
  • Organizer: The 2009 Fall Conference of The Korean Association of Immunologists
  • Place of Presentation: Seoul, Republic of Korea
  • Year and Date: 2009-11-09
• [Presentation] Enhanced skin wound healing in PDLIM2-deficient mice. (2009)
  • Author(s): Tanaka T., Kaisho T.
  • Organizer: The 9^<th> World Congress on Inflammation.
  • Place of Presentation: 東京
  • Year and Date: 2009-07-07
• [Presentation] PDLIM2欠損マウスにおける皮膚創傷治癒反応の亢進 (2008)
  • Author(s): 田中貴志、改正恒康
  • Organizer: 日本免疫学会
  • Place of Presentation: 大阪
  • Year and Date: 2008-12-02
• [Presentation] PDLIM2欠損マウスにおける皮膚創傷治癒反応の亢進 (2008)
  • Author(s): 田中貴志
  • Organizer: 第38回日本免疫学会総会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-02
• [Presentation] PDLIM2 and HSP70 cooperatively terminate Toll-like receptor-mediated NF-κB activation. (2008)
  • Author(s): Tanaka T., Kaisho T.
  • Organizer: The 10^<th> International Symposium on Dendritic Cells.
  • Place of Presentation: 神戸
• [Presentation] PDLIM2 and HSP70 cooperatively terminate Toll-like receptor-mediated NF-κB activation (2008)
  • Author(s): Takashi Tanaka
  • Organizer: The 10^<th> International Symposium on Dendritic cells
  • Place of Presentation: Kobe, JAPAN
• [Remarks] ホームページ等
  • URL: http://www.rcai.riken.jp/group/inflammatory/index.html
• [Remarks]
  • URL: http://www.rcai.riken.jp/group/inflammatory/index.html
• [Patent(Industrial Property Rights)] 創傷治癒剤及びそのスクリーニング方法 (2009)
  • Inventor(s): 田中貴志、改正恒康
  • Industrial Property Rights Holder: 独立行政法人理化学研究所
  • Filing Date: 2009-11-05
• [Patent(Industrial Property Rights)] 創傷治癒剤及びそのスクリーニング方法 (2009)
  • Inventor(s): 田中貴志、改正恒康
  • Industrial Property Rights Holder: 独立行政法人理化学研究所
  • Filing Date: 2009-11-05
  • Overseas
• [Patent(Industrial Property Rights)] 創傷治癒剤及びそのスクリーニング方法 (2009)
  • Inventor(s): 田中貴志改正恒康
  • Industrial Property Rights Holder: 独立行政法人理化学研究所
  • Industrial Property Number: 2009-254379
  • Filing Date: 2009-11-05
• [Patent(Industrial Property Rights)] 創傷治癒剤及びそのスクリーニング方法 (2009)
  • Inventor(s): 田中貴志改正恒康
  • Industrial Property Rights Holder: 独立行政法人理化学研究所
  • Filing Date: 2009-11-05
  • Overseas