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Life and disease orchestrated by lipid metabolizing enzymes

Research Project

Project/Area Number 17H04012
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General anatomy (including histology/embryology)
Research InstitutionYamagata University

Principal Investigator

Goto Kaoru  山形大学, 医学部, 教授 (30234975)

Co-Investigator(Kenkyū-buntansha) 中野 知之  山形大学, 医学部, 准教授 (00333948)
田中 俊昭  山形大学, 医学部, 助教 (70536987)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2019: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywords脂質代謝 / ジアシルグリセロールキナーゼ / 転写調節 / 酵素活性 / p53 / NF-kB / ストレス応答 / 炎症応答 / 酵素活性依存的 / アポトーシス / エネルギー代謝 / 生活習慣病 / 脂肪組織リモデリング / 褐色脂肪細胞 / 脂質代謝酵素 / 細胞応答 / 個体レベル / 高脂肪食 / 白色脂肪 / トリグリセリド / 脂肪分解酵素 / 細胞・組織 / 行動解析
Outline of Final Research Achievements

Major constituents of lipid bilayer, phospholipids, are initially produced by phosphorylation of diacylglycerol (DG). We are working on the functional analysis of DG-phosphorylating enzyme, DG kinase (DGK). In this study, we investigated regulatory mechanisms of tumor suppressor p53 and master transcription factor of inflammation NF-kB by DGKzeta and its binding partners. We found that DGKzeta enzymatic activity positively regulates p53 transcription activity whereas it negatively regulates NF-kB transcription activity. In addition, DGKzeta binding partners modulate specificity and selectivity of these transcription factors. These results suggest that DGKzeta plays an important role in the regulation of transcription factors through the enzymatic activity.

Academic Significance and Societal Importance of the Research Achievements

三大栄養素の一つである脂質は、貯蔵エネルギーとしてのみならず、生命の基本単位である細胞の外壁(細胞膜)の構成要素としても機能する。細胞膜の脂質はさらに、その合成や分解の過程において、細胞機能を調節する情報伝達物質の役割も果たす。本研究では、代表的な脂質の一つであるジアシルグリセロールの代謝酵素が、その活性を利用して、細胞核内の遺伝子転写機構を調節することを明らかにした。

Report

(4 results)
  • 2020 Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (10 results)

All 2021 2020 2018 2017 Other

All Int'l Joint Research (3 results) Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results) Presentation (4 results) (of which Invited: 1 results)

  • [Int'l Joint Research] ボローニア大学(イタリア)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] ユタ大学(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] ユタ大学(米国)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Regulation of p53 and NF-κB transactivation activities by DGKζ in catalytic activity-dependent and -independent manners2021

    • Author(s)
      Tanaka Toshiaki、Nakano Tomoyuki、Hozumi Yasukazu、Martelli Alberto M.、Goto Kaoru
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

      Volume: 1868 Issue: 4 Pages: 118953-118953

    • DOI

      10.1016/j.bbamcr.2021.118953

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Deletion of diacylglycerol kinase ε confers susceptibility to obesity via reduced lipolytic activity in murine adipocytes2018

    • Author(s)
      Nakano T, Seino K, Wakabayashi I, Stafforini DM, Topham MK, Goto K
    • Journal Title

      FASEB J.

      Volume: - Issue: 8 Pages: 4121-4130

    • DOI

      10.1096/fj.201701050r

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] DaMab-2: Anti-Human DGKα Monoclonal Antibody for Immunocytochemistry2017

    • Author(s)
      Nakano Tomoyuki、Ogasawara Satoshi、Tanaka Toshiaki、Hozumi Yasukazu、Mizuno Satoru、Satoh Eri、Sakane Fumio、Okada Naoki、Taketomi Akinobu、Honma Ryusuke、Nakamura Takuro、Saidoh Noriko、Yanaka Miyuki、Itai Shunsuke、Handa Saori、Chang Yao-Wen、Yamada Shinji、Kaneko Mika K.、Kato Yukinari、Goto Kaoru
    • Journal Title

      Monoclon. Antib. Immunodiagn. Immunother.

      Volume: 36 Issue: 4 Pages: 181-184

    • DOI

      10.1089/mab.2017.0023

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] DGKζ deletion dysregulates DNA repair mechanism2020

    • Author(s)
      Toshiaki Tanaka, Kaoru Goto
    • Organizer
      第125回日本解剖学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ε型ジアシルグリセロールキナーゼ欠損による脂肪組織リモデリングの解析-寒冷暴露による変化-2018

    • Author(s)
      中野 知之、後藤 薫
    • Organizer
      第124回日本解剖学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ジアシルグリセロール代謝不全に起因する脂肪蓄積とインスリンシグナル異常2018

    • Author(s)
      中野 知之、後藤 薫
    • Organizer
      第123回日本解剖学会総会シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] DGKε欠損は白色脂肪細胞における脂質代謝異常を惹起する2017

    • Author(s)
      中野 知之、後藤 薫
    • Organizer
      第63回日本解剖学会地方会
    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2022-01-27  

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