Analysis of the NF-kB pathway in the initial immune response under inflammatory conditions

• Project/Area Number: 15K10530
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: Yamagata University
• Principal Investigator: Kawamae Kaneyuki 山形大学, 医学部, 教授 (70254026)
• Co-Investigator(Kenkyū-buntansha): 後藤 薫 山形大学, 医学部, 教授 (30234975)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 炎症応答 / 脂質代謝酵素 / 転写活性 / 核内移行 / リン酸化 / NF-kB / p53 / 転写調節 / アポトーシス / 急性炎症応答 / 脂質性情報伝達機構 / 結合蛋白 / NF-κB / ジアシルグリセロールキナーゼ / 細胞内情報伝達機構 / TNFα

Outline of Final Research Achievements

Transcription factor NFkB plays a central role in various signaling pathways including immune response, inflammation, cell survival and death, and cancer. In the present study, we examined how zeta isoform of diacylglycerol kinase (DGK) regulates NFkB pathway. We found that after TNF-alpha stimulation DGKzeta deficiency leads to facilitated nuclear transport of NFkB p65 subunit together with its enhanced phosphorylation, thereby upregulating NFkB transcriptional activity. These results suggest that DGKzeta negatively regulates NFkB pathway and that DGKzeta downregulation may enhance inflammatory response.

Research Products

• [Journal Article] DGKζ downregulation enhances osteoclast differentiation and bone resorption activity under inflammatory conditions. (2017)
  • Author(s): Iwazaki K, Takana T, Hozumi Y, Okada M, Tsuchiya R, Iseki K, Topham MK, Kawamae K, Takagi M, Goto K
  • Journal Title: J Cellular physiol Volume: 232 Issue: 3 Pages: 617-624
  • DOI: 10.1002/jcp.25461
  • Peer Reviewed
• [Journal Article] Arachidonoyl-Specific Diacylglycerol Kinase epsilon and the Endoplasmic Reticulum (2016)
  • Author(s): Nakano T, Matsui H, Tanaka T, Hozumi Y, Iseki K, Kawamae K, Goto K
  • Journal Title: Front Cell Dev Biol Volume: 4 Pages: 132-132
  • DOI: 10.3389/fcell.2016.00132
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] DGKzeta結合蛋白NAP1-like proteins によるp53アセチル化制御を介した細胞周期およびアポトーシス制御機構の解析 (2018)
  • Author(s): 田中 俊昭、後藤 薫
  • Organizer: 第123回日本解剖学会総会
• [Presentation] Regulation of p53 and NF-kB by DGKzeta (2016)
  • Author(s): Tanaka T, Goto K
  • Organizer: The American Society for Cell Biology Annual Meeting
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2016-12-03
  • Int'l Joint Research
• [Presentation] DGKzeta 結合蛋白NAP1L1 によるNF-kB転写遺伝子Mcl-1の発現制御 (2016)
  • Author(s): 田中俊昭、後藤薫
  • Organizer: 第62日本解剖学会・東北北海道地方会
  • Place of Presentation: 帯広畜産大学（帯広）
  • Year and Date: 2016-09-03
• [Presentation] 生体ストレスを解剖する (2016)
  • Author(s): 後藤薫
  • Organizer: 第19回日本臨床救急医学会総会
  • Place of Presentation: ビッグパレットふくしま（郡山）
  • Year and Date: 2016-05-12
  • Invited
• [Presentation] ゼータ型DGKによるエネルギーセンサーAMPKの制御 (2016)
  • Author(s): 秋元 亮、田中 俊昭、八月朔日 泰和、川前 金幸、後藤 薫
  • Organizer: 第１２１回 日本解剖学会総会・全国学術集会
  • Place of Presentation: ビッグパレットふくしま（福島県郡山市）
  • Year and Date: 2016-03-28
• [Presentation] Regulation of p53 and NF-kB by diacylglycerol kinase ζ. (2015)
  • Author(s): Goto K.
  • Organizer: Fifty-Six International Symposium on “Biological Regulation and Enzyme Activity in Normal and Neoplastic Tissues”
  • Place of Presentation: Bologna, Italy
  • Year and Date: 2015-10-05
  • Int'l Joint Research / Invited
• [Presentation] DGKζ結合蛋白NAP1-like proteins によるp53アセチル化修飾はCBPおよびHDAC4との結合を介して調節される. (2015)
  • Author(s): 田中 俊昭、後藤 薫
  • Organizer: 第61日本解剖学会・東北北海道地方会
  • Place of Presentation: 盛岡市観光文化交流センター（岩手県盛岡市）
  • Year and Date: 2015-08-29