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Functional roles of the lipid second messenger metabolizing enzyme family

Research Project

Project/Area Number 24390044
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
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) FUJII SATOSHI  山形大学, 医学部, 教授 (80173384)
HOZUMI YASUKAZU  山形大学, 医学部, 准教授 (00372334)
NAKANO TOMOYUKI  山形大学, 医学部, 助教 (00333948)
TANAKA TOSHIAKI  山形大学, 医学部, 助教 (70536987)
Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2014: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2013: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2012: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Keywordsリン脂質代謝 / 細胞内局在 / 炎症応答 / 小胞体 / 免疫電顕 / 副腎 / ステロイド / カテコールアミン / ストレス / 核 / プルキンエ細胞 / ストレス応答 / アポトーシス / p53 / プロテアソーム / 小脳 / 運動学習実験 / 脂質代謝酵素 / イノシトールリン脂質 / がん細胞
Outline of Final Research Achievements

Membrane lipid turnover generates diacylglycerol (DG), which serves not only as a second messenger but also as an intermediate product of lipid metabolism. DG kinase (DGK) is an enzyme that phosphorylates DG to phosphatidic acid. This enzymatic reaction occurs ubiquitously in cells, although much of the functional role remains undetermined. In this study, we found the following results: 1) downregulation of DGKzeta upregulates an activity of the major inflammatory transcription factor NFkB, thereby enhancing an inflammatory reaction. 2) By immunogold electron microscopy, DGKepsilon is localized to the smooth endoplasmic reticulum (ER) of cerebellar Purkinje cells. 3) Three leucine residues, Leu22, L25 and L29, which form a hydrophobic patch in the N-terminus, play a necessary role in targeting of DGKepsilon to the ER.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (23 results)

All 2016 2015 2014 2013 2012

All Journal Article (11 results) (of which Peer Reviewed: 11 results,  Acknowledgement Compliant: 5 results,  Open Access: 1 results) Presentation (12 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results)

  • [Journal Article] Expression and localization of the diacylglycerol kinase family and of phosphoinositide signaling molecules in the adrenal gland.2015

    • Author(s)
      Hozumi Y, Akimoto R, Suzuki A, Otani K, Watanabe M, Goto K.
    • Journal Title

      Cell Tissue Res.

      Volume: 362 Issue: 2 Pages: 295-305

    • DOI

      10.1007/s00441-015-2199-3

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Involvement of diacylglycerol kinase B in the spine formation at distal dendrites of striatal medium spiny neurons.2015

    • Author(s)
      Hozumi Y, Kakefuda K, Yamasaki M, Watanabe M, Hara H, Goto K
    • Journal Title

      Brain Res,

      Volume: 1594 Pages: 36-45

    • DOI

      10.1016/j.brainres.2014.11.012

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of the N-terminal hydrophobic residues of DGKε in targeting the endoplasmic reticulum.2014

    • Author(s)
      Matsui H, Hozumi Y, Tanaka T, Okada M, Nakano T, Suzuki Y, Iseki K, Kakehata S, Topham MK, Goto K.
    • Journal Title

      Biochim Biophys Acta Molecular and Cell Biology of Lipids

      Volume: 1842 Issue: 10 Pages: 1440-1450

    • DOI

      10.1016/j.bbalip.2014.07.007

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Cellular expression and localization of DGKζ-interacting NAP1-like proteins in the brain and functional implications under hypoxic stress.2014

    • Author(s)
      Takahashi N, Hozumi Y, Tanaka T, Okada M, Iseki K, Hayasaka K, Goto K.
    • Journal Title

      Histochem Cell Biol

      Volume: 142 Issue: 5 Pages: 461-471

    • DOI

      10.1007/s00418-014-1226-x

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] DGKζ under stress conditions: "To be nuclear or cytoplasmic, that is the question"2014

    • Author(s)
      Goto K, Tanaka T, Nakano T, Okada M, Hozumi Y, Topham MK, Martelli AM.
    • Journal Title

      Advances in Biological Regulation

      Volume: 54 Pages: 242-253

    • DOI

      10.1016/j.jbior.2013.08.007

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Expression of mRNAs for the diacylglycerol kinase family in immune cellsduring an inflammatory reaction2014

    • Author(s)
      Yamamoto M, Tanaka T, Hozumi Y, Saino-Saito S, Nakano T, Tajima K, Kato T, Goto K.
    • Journal Title

      Biomedical Research

      Volume: 35 Issue: 1 Pages: 61-68

    • DOI

      10.2220/biomedres.35.61

    • NAID

      130004903860

    • ISSN
      0388-6107, 1880-313X
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Knockdown of Sec8 enhances the binding affinity of c-Jun N-terminal kinase (JNK)-interacting protein 4 for mitogen-activated protein kinase kinase 4 (MKK4) and suppresses the phosphorylation of MKK4, p38, and JNK, thereby inhibiting apoptosis.2014

    • Author(s)
      Tanaka T, Iino M, Goto K.
    • Journal Title

      FEBS Journal

      Volume: 281 Issue: 23 Pages: 5237-5250

    • DOI

      10.1111/febs.13063

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytoplasmic localization of DGKζ exerts a protective effect against p53-mediated cytotoxicity.2013

    • Author(s)
      Tanaka T, Okada M, Hozumi Y, Tachibana K, Kitanaka C, Hamamoto Y, Martelli AM, Topham MK, Iino M, Goto K.
    • Journal Title

      J Cell Sci.

      Volume: 126(Pt 13) Pages: 2785-2797

    • DOI

      10.1242/jcs.118711

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Distinct expression and localization of diacylglycerol kinase isozymes in rat retina2013

    • Author(s)
      Hozumi, Y.
    • Journal Title

      J. Histochem. Cytochem.

      Volume: 未定 Issue: 6 Pages: 462-476

    • DOI

      10.1369/0022155413483574

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The emerging multiple roles of nuclear Akt2012

    • Author(s)
      Martelli AM, Tabellini G, Bressanin D, Ognibene A, Goto K, Cocco L, Evangelisti C.
    • Journal Title

      Biochim Biophys Acta

      Volume: 1823 Issue: 12 Pages: 2168-78

    • DOI

      10.1016/j.bbamcr.2012.08.017

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DGKζ is degraded through the cytoplasmic ubiquitin-proteasome system under excitotoxic conditions, which causes neuronal apoptosis because of aberrant cell cycle reentry2012

    • Author(s)
      Okada M, Hozumi Y, Tanaka T, Suzuki Y, Yanagida M, Araki Y, Evangelisti C, Yagisawa H, Topham MK, Martelli AM, Goto K.
    • Journal Title

      Cell Signal

      Volume: 24 Issue: 8 Pages: 1573-82

    • DOI

      10.1016/j.cellsig.2012.03.021

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] 副腎におけるイノシトールリン脂質代謝関連分子の発現局在解析.2016

    • Author(s)
      八月朔日 泰和、後藤 薫
    • Organizer
      第121回 日本解剖学会総会・全国学術集会
    • Place of Presentation
      ビッグバレットふくしま(福島県郡山市)
    • Year and Date
      2016-03-28
    • Related Report
      2015 Annual Research Report
  • [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
      ボローニア、イタリア
    • Year and Date
      2015-10-05
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Cellular processes mediated by a lipid-metabolizing enzyme diacylglycerol kinase (DGK) family2015

    • Author(s)
      Kaoru Goto
    • Organizer
      第120回 日本解剖学会総会
    • Place of Presentation
      神戸ポートピアアイランド、神戸
    • Year and Date
      2015-03-21 – 2015-03-23
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Involvement of diacylglycerol kinase β in the spine formation at distal dendrites of striatal medium spiny neurons2015

    • Author(s)
      Yasukazu Hozumi, Kaoru Goto
    • Organizer
      第120回 日本解剖学会総会
    • Place of Presentation
      神戸ポートピアアイランド、神戸
    • Year and Date
      2015-03-21 – 2015-03-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] Diacylglycerol kinase ε-KO mice are susceptible to high fat diet-induced obesity and adipose tissue-specific insulin resistance.2014

    • Author(s)
      Nakano T, Goto K
    • Organizer
      The American Society for Cell Biology Annual Meeting
    • Place of Presentation
      Philadelphia Convention Center, Philadelphia, USA
    • Year and Date
      2014-12-06 – 2014-12-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] Cytoplasmic translocation of DGKzeta exerts a protective effect against p53-mediated cytotoxicity.2014

    • Author(s)
      Goto K,Tanaka T
    • Organizer
      The American Society for Cell Biology Annual Meeting
    • Place of Presentation
      Philadelphia Convention Center, Philadelphia, USA
    • Year and Date
      2014-12-06 – 2014-12-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] 一酵素ファミリーから見た生命現象―脂質性二次メッセンジャー代謝酵素ジアシルグリセロールキナーゼの機能解析2014

    • Author(s)
      後藤薫
    • Organizer
      第60日本解剖学会・東北北海道地方会
    • Place of Presentation
      福島県立医大、福島
    • Year and Date
      2014-09-06 – 2014-09-07
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] DGKζ 結合蛋白NAP1-like proteins によるp21および 細胞周期の制御2014

    • Author(s)
      田中俊昭、後藤薫
    • Organizer
      第119回日本解剖学会総会
    • Place of Presentation
      自治医科大学(栃木)
    • Related Report
      2013 Annual Research Report
  • [Presentation] イプシロン型ジアシルグリセロールキナーゼの形態学的機能解析2014

    • Author(s)
      八月朔日泰和、後藤薫
    • Organizer
      第119回日本解剖学会総会
    • Place of Presentation
      自治医科大学(栃木)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Cytoplasmic localization of diacylglycerol kinase ζ exerts a protective effect against p53-mediated cytotoxicity2013

    • Author(s)
      Goto K,Tanaka T
    • Organizer
      44th International Symposium on “Biological Regulation and Enzyme Activity in Normal and Neoplastic Tissues”
    • Place of Presentation
      University of Bologna (Italy)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] DGK5結合蛋白NAP1-like proteins による細胞周期制御因子p21を介したサイクリン発現制御機構の解析2013

    • Author(s)
      田中俊昭、後藤薫
    • Organizer
      第118回 日本解剖学会総会
    • Place of Presentation
      香川大学(高松)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Cytoplasmic localization of diacylglycerol kinase zeta suppresses p53 ind uction after DNA damage.2012

    • Author(s)
      Tanaka T, Goto K
    • Organizer
      42th Annual Meeting of Neuroscience
    • Place of Presentation
      Convention Center(New Orleans, USA)
    • Related Report
      2012 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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