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Molecular basis fo protein-crosslinking reaction by transglutaminase focusing on aberrant regulation

Research Project

Project/Area Number 26292192
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Applied molecular and cellular biology
Research InstitutionNagoya University

Principal Investigator

Hitomi Kiyotaka  名古屋大学, 創薬科学研究科, 教授 (00202276)

Co-Investigator(Renkei-kenkyūsha) HASHIMOTO Hisashi  名古屋大学, 生物機能利用研究センター, 助教 (30359757)
YAMANISHI Kiyofumi  兵庫医科大学, 医学部, 教授 (10182586)
Kuroda Syunichi  大阪大学, 大学院理学研究科(産業科学研究所), 教授 (60263406)
Research Collaborator TATSUKAWA Hideki  名古屋大学, 大学院創薬科学研究科, 助教
KINOSHITA Masato  京都大学, 大学院農学研究科, 助教
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2016: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2015: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2014: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Keywords酵素 / カルシウム / 表皮 / 線維症 / 皮膚表皮
Outline of Final Research Achievements

Enzymatic cross-linking reaction of proteins is carried out by transglutaminase, which consists of enzyme family in human. By the enzymatic reaction, several essential protein modifications are accomplished such as blood coagulation and epidermis formation. The enzymatic reaction is critically regulated and contribute to homeostasis. However, in the case of aberrant expression, activation, or reaction of the transglutaminase, cellular and/or tissue damage occur that will bring several kinds of diseases in human.
In order to clarify the aberrant enzymatic reactions and their products at the level of cell, tissue, and body, we investigated the variation of the enzymatic activities and substrates (products), expression pattern of the enzymes in several tissues: liver, kidney, epidermis at disease condition. Furthermore, using medaka as the model organism, we established the gene-deficient fish of transglutaminase as diseaes model.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (41 results)

All 2017 2016 2015 2014

All Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 9 results,  Acknowledgement Compliant: 7 results,  Open Access: 3 results) Presentation (30 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results) Book (1 results)

  • [Journal Article] FRET-based detection of isozyme-specific activities of transglutaminases.2017

    • Author(s)
      Tatsukwa H, Liu H, Oba S, Kamiya N, Nakanishi Y, Hitomi K
    • Journal Title

      Amino Acids

      Volume: 49 Issue: 3 Pages: 615-623

    • DOI

      10.1007/s00726-016-2322-0

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Characterization of medaka orthologue of human transglutaminase 2 (OlTGT)2017

    • Author(s)
      Takada Y., Watanabe Y., Okuya K., Tatsukawa H., Hashimoto H, Hitomi K.
    • Journal Title

      Biochem. Biotechnol. Biosci.

      Volume: 81 Issue: 3 Pages: 469-474

    • DOI

      10.1080/09168451.2016.1256757

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Global identification and analysis of isozyme-specific possible substrates crosslinked by transglutaminases using their substrate peptides in mouse liver fibrosis.2017

    • Author(s)
      Tatsukawa H., Tan Y., Otsu R., Nakagawa H., Hitomi K
    • Journal Title

      Sci. rep

      Volume: 22 Issue: 1 Pages: 45049-45049

    • DOI

      10.1038/srep45049

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Analysis on transglutaminase 1 and its substrates using specific substrate peptide in cultured keratinocytes.2016

    • Author(s)
      Yamane M., Sugimura K., Kawasaki H., Tatsukawa H., Hitomi K.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 478 Issue: 1 Pages: 343-348

    • DOI

      10.1016/j.bbrc.2016.07.051

    • NAID

      120005893262

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] トランスグルタミナーゼとポリアミン2016

    • Author(s)
      人見清隆
    • Journal Title

      ポリアミン

      Volume: 3 Pages: 8-13

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Biochemical Characterization of Medaka (Oryzias latipes) Transglutaminases, OlTGK1 and OlTGK2, as Orthologues of Human Keratinocyte-Type Transglutaminase.2015

    • Author(s)
      Kikuta A, Furukawa E, Ogawa R, Suganuma N, Saitoh M, Nishimaki T, Katsumura T, Oota H, Kawamoto T, Tatsukawa H, Hashimoto H, Hitomi K.
    • Journal Title

      PLoS One.

      Volume: 10 Issue: 12 Pages: 1-13

    • DOI

      10.1371/journal.pone.0144194

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Distribution of transglutaminase family members in mouse whole body sections.2015

    • Author(s)
      Tatsukawa H, Abe N, Ohashi S, Hitomi K.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 467 Issue: 4 Pages: 1046-51

    • DOI

      10.1016/j.bbrc.2015.10.001

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Early response as shown by enhancement of transglutaminase 1 expression after cisplatin-induced acute kidney injury.2015

    • Author(s)
      Furukawa K, Yamane M, Tatsukawa H, Hitomi K.
    • Journal Title

      Arch Biochem Biophys.

      Volume: 586 Pages: 27-32

    • DOI

      10.1016/j.abb.2015.09.021

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Factor XIII-A transglutaminase acts as a switch between preadipocyte proliferation and differentiation.2014

    • Author(s)
      Myneni VD, Hitomi K., Kaartinen M.
    • Journal Title

      Blood

      Volume: 124 Issue: 8 Pages: 1344-1353

    • DOI

      10.1182/blood-2013-12-543223

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transglutaminase activity is decreased in large arteries from hypertensive rats, compared to normotensive controls.2014

    • Author(s)
      Petersen-Jones HG, Johnson KB, Hitomi K, Tykocki NR, Thompson JM, Watts SW.
    • Journal Title

      Am J Physiol Heart Circ Physiol.

      Volume: 308 Issue: 6 Pages: H592-H602

    • DOI

      10.1152/ajpheart.00402.2014

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Presentation] 血液凝固に関するメダカトランスグルタミナーゼの解析と遺伝子変異個体の作製2017

    • Author(s)
      人見清隆、堀水里麻、渡邊優子、橋本寿史、辰川英樹、
    • Organizer
      農芸化学会大会
    • Place of Presentation
      京都女子大学
    • Related Report
      2016 Annual Research Report
  • [Presentation] 肝線維化におけるタンパク質架橋化酵素の役割2017

    • Author(s)
      中川晴加、辰川英樹、人見清隆
    • Organizer
      農芸化学会大会
    • Place of Presentation
      京都女子大学
    • Related Report
      2016 Annual Research Report
  • [Presentation] モデル生物としてメダカを用いたタンパク質架橋化酵素の生理的機能解析2016

    • Author(s)
      奥谷冬穂、渡邊優子、辰川英樹、木下政人、橋本寿史、人見清隆
    • Organizer
      小型魚類研究会
    • Place of Presentation
      岡崎カンファレンスセンター
    • Year and Date
      2016-08-20
    • Related Report
      2016 Annual Research Report
  • [Presentation] タンパク質架橋化酵素の生理的意義を高反応性基質配列で解析する2016

    • Author(s)
      人見清隆
    • Organizer
      生物工学会中部支部例会
    • Place of Presentation
      名古屋大学
    • Year and Date
      2016-08-05
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Transglutaminases in the medaka, fish as a model animal: biochemical characterization of mammalian orthologues and establishment of gene-deficient fish2016

    • Author(s)
      人見清隆、堀水里麻、奥谷冬穂、渡邊優子、辰川英樹
    • Organizer
      ゴードン国際会議 Gordon Research Conference
    • Place of Presentation
      Spain
    • Year and Date
      2016-07-10
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Comprehensive approach for identification and analysis of2016

    • Author(s)
      辰川英樹、大津里紗、人見清隆
    • Organizer
      ゴードン国際会議 Gordon Research Conference
    • Place of Presentation
      Spain
    • Year and Date
      2016-07-10
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification and characterization of crosslinked substrates2016

    • Author(s)
      脇田峻資、辰川英樹、人見清隆
    • Organizer
      ゴードン国際会議 Gordon Research Conference
    • Place of Presentation
      Spain
    • Year and Date
      2016-07-10
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] タンパク質架橋化酵素の高反応性基質配列を用いた病態解析2016

    • Author(s)
      人見清隆
    • Organizer
      日本農芸化学会中四国支部シンポジウム
    • Place of Presentation
      岡山大学農学部
    • Year and Date
      2016-05-20
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] タンパク質架橋化酵素トランスグルタミナーゼで病態を診断する2016

    • Author(s)
      人見清隆
    • Organizer
      日本農芸化学会 シンポジウム
    • Place of Presentation
      札幌
    • Year and Date
      2016-03-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] ゲノム編集技術を用いたメダカにおける遺伝子変異個体の作製2016

    • Author(s)
      奥谷冬穂、高田佑紀、辰川英樹、橋本寿史、人見清隆
    • Organizer
      生化学会中部支部例会
    • Place of Presentation
      三重大学
    • Related Report
      2016 Annual Research Report
  • [Presentation] 腎臓の線維化進行に伴うタンパク質架橋化修飾の役割2016

    • Author(s)
      脇田峻資、大津里沙、辰川英樹、人見清隆
    • Organizer
      生化学会中部支部例会
    • Place of Presentation
      三重大学
    • Related Report
      2016 Annual Research Report
  • [Presentation] タンパク質架橋化反応を検出する新規バイオセンサー開発2016

    • Author(s)
      辰川英樹,劉紅紅、大庭将太、人見清隆
    • Organizer
      生化学会中部支部例会
    • Place of Presentation
      三重大学
    • Related Report
      2016 Annual Research Report
  • [Presentation] タンパク質架橋化酵素の高反応性基質配列を用いた病態解析2016

    • Author(s)
      人見清隆
    • Organizer
      日本農芸化学会中四国若手シンポジウム
    • Place of Presentation
      岡山大学
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] タンパク質架橋化酵素トランスグルタミナーゼの高反応性ペプチドの多面的活用2016

    • Author(s)
      人見清隆
    • Organizer
      生物工学会中部支部
    • Place of Presentation
      名古屋大学
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 腎線維化に伴い架橋される新規基質タンパク質S100-A8およびS100-A9の機能解析2016

    • Author(s)
      脇田峻資、大津里紗、辰川英樹、人見清隆
    • Organizer
      生化学会大会
    • Place of Presentation
      東北大学
    • Related Report
      2016 Annual Research Report
  • [Presentation] 肝線維化に伴い架橋される基質タンパク質の網羅的同定および解析2016

    • Author(s)
      辰川英樹、大津里紗、人見清隆
    • Organizer
      生化学会大会
    • Place of Presentation
      東北大学
    • Related Report
      2016 Annual Research Report
  • [Presentation] メダカを用いた遺伝子変異個体の作製による組織型トランスグルタミナーゼの機能解析2016

    • Author(s)
      奥谷冬穂、渡邊優子、辰川英樹、木下政人、橋本寿史、人見清隆
    • Organizer
      分子生物学会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2016 Annual Research Report
  • [Presentation] モデル生物としてメダカを用いたタンパク質架橋化酵素の生理的機能解析2015

    • Author(s)
      堀水里麻、辰川英樹、木下政人、橋本寿史、人見清隆
    • Organizer
      第88回日本生化学会第38回分子生物合同大会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2015-12-03
    • Related Report
      2015 Annual Research Report
  • [Presentation] ヒト表皮細胞分化に伴うタンパク質架橋化酵素とその基質群の発現解析2015

    • Author(s)
      椙村佳代子、山根美樹、川崎寛子、辰川英樹、人見清隆
    • Organizer
      第88回日本生化学会第38回分子生物合同大会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2015-12-03
    • Related Report
      2015 Annual Research Report
  • [Presentation] Simple and sensitive detection system of the enzymatic activity for analyses of diseases related to transglutaminases2015

    • Author(s)
      人見清隆
    • Organizer
      第88回日本生化学会 第38回分子生物合同大会ワークショップ
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2015-12-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] 線維症疾患におけるトランスグルタミナーゼの機能解析2015

    • Author(s)
      大津理沙、谷優治、辰川英樹、人見清隆
    • Organizer
      第88回日本生化学会第38回分子生物合同大会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2015-12-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] モデル生物としてメダカのタンパク質架橋化酵素ファミリーとその機能に関する解析2015

    • Author(s)
      高田祐紀、奥谷冬穂、辰川秀樹、橋本寿史、人見清隆
    • Organizer
      日本農芸化学会関西中部合同大会
    • Place of Presentation
      富山大学
    • Year and Date
      2015-09-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] 腎臓の線維化進行に伴うタンパク質架橋化修飾の役割2015

    • Author(s)
      大津理沙、谷優治、脇田崚資、辰川秀樹、人見清隆
    • Organizer
      日本農芸化学会関西中部合同大会
    • Place of Presentation
      富山大学
    • Year and Date
      2015-09-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] 表皮型タンパク質架橋化酵素に対する高反応性基質ペプチドの活用法2015

    • Author(s)
      山根美樹、椙村佳代子、辰川秀樹、人見清隆
    • Organizer
      日本農芸化学会関西中部合同大会
    • Place of Presentation
      富山大学
    • Year and Date
      2015-09-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] タンパク質架橋化酵素の組織分布解析メダカにおける類似遺伝子群の解析2015

    • Author(s)
      古川 エリ、菊田綾華、辰川英樹、人見清隆
    • Organizer
      第135回日本薬学会年会
    • Place of Presentation
      神戸学院大学
    • Year and Date
      2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] 蛋白質架橋反応を捉える新規FRETプローブの開発2015

    • Author(s)
      劉 紅紅、辰川英樹、人見清隆
    • Organizer
      第136回日本薬学会年会
    • Place of Presentation
      神戸学院大学
    • Year and Date
      2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] 皮膚表皮細胞内でトランスグルタミナーゼにより架橋化されるタンパク質の解析2014

    • Author(s)
      山根 美樹、椙村佳代子、辰川英樹、人見清隆
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 皮膚表皮形成に必須な蛋白質架橋化酵素のメダカにおける類似遺伝子群の解析2014

    • Author(s)
      菊田 紋華、古川エリ、橋本寿史、辰川英樹、人見清隆
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 肝線維症の病態形成における架橋化反応の役割2014

    • Author(s)
      谷 優治、辰川英樹、人見清隆
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 組織型タンパク質架橋化酵素のメダカにおける相同遺伝子の解析2014

    • Author(s)
      高田佑紀、菊田綾華、橋本寿史、辰川英樹、人見清隆
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2014-10-17
    • Related Report
      2014 Annual Research Report
  • [Book] Trasnglutaminase (Editor)2016

    • Author(s)
      Hitomi K, Kojima S., Fesus L.
    • Total Pages
      391
    • Publisher
      Springer
    • Related Report
      2015 Annual Research Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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