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Molecular basis of protein cross-linking reactions for cellular functions

Research Project

Project/Area Number 23380200
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
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) 小嶋 聡一  独立行政法人理化学研究所, ライフサイエンス技術基盤研究センター (10202061)
秋山 真志  名古屋大学, 大学院・医学系研究科 (60222551)
Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥19,890,000 (Direct Cost: ¥15,300,000、Indirect Cost: ¥4,590,000)
Fiscal Year 2013: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2012: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2011: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywords酵素 / 蛋白質架橋 / 細胞機能
Research Abstract

Transglutaminases are the enzymes that catalyze protein cross-linking or modification via peptide-bound glutamine residues. These reactions are essential for the multiple biological processes such as blood coagulation, skin epidermis formation and apoptosis. In order to elucidate the physiological roles and expression sites on mammals, using highly reactive substrate peptides (obtained by us for these years), we analyzed expression pattern and established identification system of possible substrates. In the studies, expressions for RNA, protein (using antibody), in situ enzymatic activity were investigated. Furthermore, establishment of FRET system to detect intracellular activity was attempted. As a result, in vitro system was successful. In addition, Medaka (Oryzias latepis) as a model animal, was analyzed for the orthologues of transglutaminases: biochemical data and establishment of a couple of genetic loss fish was produced.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (53 results)

All 2013 2012 2011 Other

All Journal Article (11 results) (of which Peer Reviewed: 9 results) Presentation (40 results) Remarks (2 results)

  • [Journal Article] Phage-displayed peptide library screening for preferred human substrate peptide sequences for transglut aminase 72013

    • Author(s)
      Kurmaoto K, Yamasaki R, Hitomi K (他2名)
    • Journal Title

      Arch. Biophys. Biochem

      Volume: 537 Issue: 1 Pages: 138-143

    • DOI

      10.1016/j.abb.2013.07.010

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Variations in both TG1 and TG2 isozyme-specific in situ activities and protein expressions during mouse embryonic development2013

    • Author(s)
      Itoh M, Tatsukawa H. Kojima S., Hitomi K (他2名)
    • Journal Title

      J. Histochem. Cytochem

      Volume: 61 Issue: 11 Pages: 793-801

    • DOI

      10.1369/0022155413501676

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Kaartinen M Transglutaminase activity arising from Factor XIIIA is required for stabilization and conversion of plasma fibronectin into matrix in osteoblast cultures2013

    • Author(s)
      Cui C, Wang S, Myneni VD, Hitomi K
    • Journal Title

      Bone

      Volume: 59 Pages: 127-38

    • DOI

      10.1016/j.bone.2013.11.006

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Transglutaminase and Factor XIII catalyze distinct subs trates in differentiating osteoblastic cell line2013

    • Author(s)
      Watanabe K, Tsunoda, K, Itoh M, Fukui M, Mori H, Hitomi K
    • Journal Title

      Amino Acids

      Volume: (印刷中)(on line)(公開中) Issue: 1 Pages: 209-214

    • DOI

      10.1007/s00726-011-1131-8

    • Related Report
      2013 Final Research Report 2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of a highly reactive peptide for TG6 : Detection of its trans glutaminase activity in the skin epider mis using the peptide2013

    • Author(s)
      Fukui M, Kuramoto K, Hitomi K (他4名)
    • Journal Title

      FEBS J

      Volume: 280 Issue: 6 Pages: 1420-1429

    • DOI

      10.1111/febs.12133

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A distinct effect of transient and sustained upregulation of cellular factor XIII in the goldfish retina and optic nerve on optic nerve regeneration.2012

    • Author(s)
      Sugitani, et al.
    • Journal Title

      Neurochemistry International

      Volume: 61(3) Issue: 3 Pages: 423-32

    • DOI

      10.1016/j.neuint.2012.06.004

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Watts SW Vena cava and aortic smooth muscle cells exp ress transglutaminases 1 and 4 in addit ion to transglutaminase 22012

    • Author(s)
      Johnson B, Hitomi K
    • Journal Title

      Am J. Physiol Heart and Circ. Physiol

      Volume: 302 Issue: 7 Pages: H1355-H1366

    • DOI

      10.1152/ajpheart.00918.2011

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] タンパク質架橋化酵素の高反応性基質の探索と活用2012

    • Author(s)
      人見清隆
    • Journal Title

      バイオテクノロジーとバイオインダストリー

      Volume: 70 Pages: 442-447

    • NAID

      10031127513

    • Related Report
      2013 Final Research Report
  • [Journal Article] Knocking-in the R142C mutation in transglutaminase 1 disrupts the stratum corneum barrier and postnatal survival of mice2012

    • Author(s)
      Nakazawa N, Yamamoto M., Hitomi K, Yamanishi K., 他10名
    • Journal Title

      Journal of Dermatological Science

      Volume: 65 Issue: 3 Pages: 196-206

    • DOI

      10.1016/j.jdermsci.2011.12.011

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] タンパク質架橋化酵素の高反応性基質の探索と活用2012

    • Author(s)
      人見清隆
    • Journal Title

      バイオサイエンスとバイオインダストリー

      Volume: 70 Pages: 442-447

    • NAID

      10031127513

    • Related Report
      2012 Annual Research Report
  • [Journal Article] Hornerin is a component of the epidermal comified cell envelopes2011

    • Author(s)
      Henry, J, Hitomi, K, Simon M, 他10名
    • Journal Title

      FASEB Journal

      Volume: 25 Issue: 5 Pages: 1567-1576

    • DOI

      10.1096/fj.10-168658

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] モデル生物としてのメダカにおけるタンパク質架橋化酵素ファミリーに関する解析モデル生物としてのメダカにおけるタンパク質架橋化酵素ファミリーに関する解析2013

    • Author(s)
      小河亮太, 辰川英樹, 人見清隆 (他3名)
    • Organizer
      第86回日本生化学会大会 (鈴木紘一メモリアル賞受賞)
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2013-09-01
    • Related Report
      2013 Final Research Report
  • [Presentation] Applications of the highly reactive substrate peptides for transglutaminases : Diagnostic visualization2013

    • Author(s)
      人見清隆
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] Highly reactive substrate peptides for transglutaminase family2013

    • Author(s)
      人見 清隆, 辰川 英樹
    • Organizer
      第36回日本分子生物学会
    • Place of Presentation
      神戸ポートアイランド
    • Related Report
      2013 Final Research Report
  • [Presentation] 高反応性基質ペプチドを用いた腎臓におけるタンパク質架橋化酵素の活性検出2013

    • Author(s)
      古川健太郎, 人見清隆 (他3名)
    • Organizer
      第36回日本分子生物学会
    • Place of Presentation
      神戸ポートアイランド
    • Related Report
      2013 Final Research Report
  • [Presentation] Applications of the higly reactive substrate peptides for transglutaminases: Diagnostic visualization2013

    • Author(s)
      人見清隆
    • Organizer
      第86回日本生化学会大会インターナショナルセッション
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] Higly reactive substrate peptides for transglutaminase family2013

    • Author(s)
      人見清隆、辰川英樹
    • Organizer
      第36回日本分子生物学会大会ワークショップ
    • Place of Presentation
      神戸国際会議場
    • Related Report
      2013 Annual Research Report
  • [Presentation] モデル生物としてのメダカにおけるタンパク質架橋化酵素ファミリーに関する解析2013

    • Author(s)
      小河亮太、渡邉優子、菅沼名津季、菊田紋華、辰川英樹、人見清隆
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] 高反応性基質ペプチドを用いた腎臓におけるタンパク質架橋化酵素の活性検出2013

    • Author(s)
      古川健太郎、山崎梨沙、山根美樹、、辰川英樹、人見清隆
    • Organizer
      第36回日本分子生物学会大会
    • Place of Presentation
      神戸国際会議場
    • Related Report
      2013 Annual Research Report
  • [Presentation] 高等動物におけるタンパク質架橋化酵素ファミリーの新規アイソザイムの組織分布に関する解析2013

    • Author(s)
      清水由隆
    • Organizer
      日本農芸化学会
    • Place of Presentation
      仙台
    • Related Report
      2012 Annual Research Report
  • [Presentation] モデル生物としてのメダカにおけるタンパク質架橋化酵素ファミリーに関する解析2013

    • Author(s)
      小河亮太
    • Organizer
      日本農芸化学会
    • Place of Presentation
      仙台
    • Related Report
      2012 Annual Research Report
  • [Presentation] 皮膚表皮におけるタンパク質架橋化酵素の基質ペプチド探索と関連疾患診断への活用2013

    • Author(s)
      人見清隆
    • Organizer
      日本薬学会
    • Place of Presentation
      横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] Identification and applications of the highly reactive substrate peptides for transglutaminases2012

    • Author(s)
      Hitomi K
    • Organizer
      Gordon Research Conference
    • Place of Presentation
      Davidson College (USA)
    • Year and Date
      2012-07-21
    • Related Report
      2013 Final Research Report
  • [Presentation] Identification and application of highly reactive peptide substrate for mammalian transglutaminas, a protein cross-linking enzyme2012

    • Author(s)
      Hitomi K
    • Organizer
      Japan-China-korea Joint symposium on Enzyme Engineering
    • Place of Presentation
      金沢
    • Year and Date
      2012-05-29
    • Related Report
      2013 Final Research Report 2012 Annual Research Report
  • [Presentation] トランスグルタミナーゼが触媒するタンパク質のポリアミン修飾による生理機能の調節2012

    • Author(s)
      人見清隆
    • Organizer
      日本農芸化学会大会
    • Place of Presentation
      京都女子大学
    • Year and Date
      2012-03-25
    • Related Report
      2013 Final Research Report
  • [Presentation] トランスグルタミナーゼが触媒するタンパク質のポリアミン修飾による生理機能の調節2012

    • Author(s)
      人見清隆
    • Organizer
      日本農芸化学会(大会シンポジウム)
    • Place of Presentation
      京都女子大学(招待講演)
    • Year and Date
      2012-03-25
    • Related Report
      2011 Annual Research Report
  • [Presentation] ヒト前立腺型タンパク質架橋化酵素の発現と前立腺由来タンパク質の基質配列解析2012

    • Author(s)
      樋口幾, 人見清隆 (他2名)
    • Organizer
      日本農芸化学会大会
    • Place of Presentation
      京都女子大学
    • Year and Date
      2012-03-24
    • Related Report
      2013 Final Research Report 2011 Annual Research Report
  • [Presentation] モデル生物としてのメダカ(Oryzias latipes) におけるタンパク質架橋化酵素の解析2012

    • Author(s)
      斉藤麻衣, 人見清隆 (他3名)
    • Organizer
      日本農芸化学会大会
    • Place of Presentation
      京都女子大学
    • Year and Date
      2012-03-24
    • Related Report
      2013 Final Research Report
  • [Presentation] モデル生物としてのメダカ(Oryzias latipes)におけるタンパク質架橋化酵素の解析2012

    • Author(s)
      斉藤麻衣、樋口幾、福井美奈、伊藤みほ、人見清隆
    • Organizer
      日本農芸化学会大会
    • Place of Presentation
      京都女子大学
    • Year and Date
      2012-03-24
    • Related Report
      2011 Annual Research Report
  • [Presentation] モデル生物としてのメダカにおけるタンパク質架橋化酵素の欠損変異体の取得と解析2012

    • Author(s)
      斎藤麻衣, 人見清隆 (他4名)
    • Organizer
      日本生化学会大会
    • Place of Presentation
      福岡国際会議場
    • Related Report
      2013 Final Research Report
  • [Presentation] モデル生物としてのメダカにおけるタンパク質架橋化酵素ファミリーの生化学的解析2012

    • Author(s)
      菅沼名津季, 人見清隆 (他4名)
    • Organizer
      日本生化学会大会
    • Related Report
      2013 Final Research Report
  • [Presentation] 皮膚表皮に存在する新規タンパク質架橋化酵素 TG6 の高反応性基質配列の解析2012

    • Author(s)
      山崎梨沙, 人見清隆 (他4名)
    • Organizer
      日本生化学会大会
    • Related Report
      2013 Final Research Report
  • [Presentation] Identification and applications of the highly reactive substrate peptides for transglutaminases2012

    • Author(s)
      Kiyotaka Hitomi
    • Organizer
      Gordon Research Conference
    • Place of Presentation
      Davidson College (USA)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Expression of tranglutaminase 4 and screening of its preferred substrate sequences2012

    • Author(s)
      Iku Higuchi
    • Organizer
      Gordon Research Conference
    • Place of Presentation
      Davidson College (USA)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Detection of in situ activities of transglutaminases using highly reactive substrate peptides in mouse embryo2012

    • Author(s)
      Miho Itoh
    • Organizer
      Gordon Research Conference
    • Place of Presentation
      Davidson College (USA)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Expression of tranglutaminase 4 and screening of its preferred substrate sequences using phage-display peptide2012

    • Author(s)
      Iku Higuchi
    • Organizer
      動物細胞工学会国際大会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Annual Research Report
  • [Presentation] モデル生物としてのメダカにおけるタンパク質架橋化酵素の欠損変異体の取得と解析2012

    • Author(s)
      斉藤麻衣
    • Organizer
      日本生化学会大会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] モデル生物としてのメダカにおけるタンパク質架橋化酵素ファミリーの生化学的解析2012

    • Author(s)
      菅沼名津季
    • Organizer
      日本生化学会大会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] 皮膚表皮に存在する新規タンパク質架橋化酵素TG6の高反応性基質配列の解析2012

    • Author(s)
      山崎梨沙
    • Organizer
      日本生化学会大会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] 新規なタンパク質架橋化酵素TG7における高反応性基質配列の解析2012

    • Author(s)
      鞍本克真
    • Organizer
      日本生化学会大会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] 機能未知な前立腺型タンパク質架橋化酵素の発現と精製および高反応性基質配列の探索2012

    • Author(s)
      樋口 幾
    • Organizer
      日本生化学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] Characterization of medaka transglutaminases, a protein cross-linking enzyme family2011

    • Author(s)
      斉藤麻衣、伊藤みほ、人見清隆
    • Organizer
      Startegic Meeting for Medaka Reasearch
    • Place of Presentation
      Okazaki Conference Center, Aichi
    • Year and Date
      2011-11-23
    • Related Report
      2011 Annual Research Report
  • [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基質配列の探索と多面的活用2011

    • Author(s)
      人見清隆
    • Organizer
      酵素工学研究会
    • Place of Presentation
      山上会館(東京)
    • Year and Date
      2011-09-29
    • Related Report
      2013 Final Research Report
  • [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基質配列の探索と多面的活用2011

    • Author(s)
      人見清隆
    • Organizer
      酵素工学研究会
    • Place of Presentation
      東京大学山上会館(招待講演)
    • Year and Date
      2011-09-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] 蛋白質架橋化酵素ファミリーの新規アイソザイムの発現解析2011

    • Author(s)
      清水由隆、福井美奈、伊藤みほ、人見清隆
    • Organizer
      日本生化学会大会
    • Place of Presentation
      京都国際会議場
    • Year and Date
      2011-09-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] 新規なヒト蛋白質架橋化酵素アイソザイムの高反応性基質配列の解析2011

    • Author(s)
      鞍本克真、福井美奈、伊藤みほ、人見清隆
    • Organizer
      日本生化学会大会
    • Place of Presentation
      京都国際会議場
    • Year and Date
      2011-09-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] タンパク質架橋化酵素の蛍光標識高反応性基質ペプチドを用いたマウス胎児組織2011

    • Author(s)
      伊藤みほ、川本忠文、人見清隆
    • Organizer
      日本生化学会大会
    • Place of Presentation
      京都国際会議場
    • Year and Date
      2011-09-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] Identification of the preferred substrate sequences for transglutaminase and utility for detection of activity in an isozyme-specific manner2011

    • Author(s)
      人見 清隆
    • Organizer
      日本生化学会大会シンポジウム
    • Place of Presentation
      京都国際会議場
    • Year and Date
      2011-09-21
    • Related Report
      2013 Final Research Report
  • [Presentation] Identification of the preferred substrate sequences for transglutaminase and utility for detection of activity in an isozyme-specific manner2011

    • Author(s)
      人見清隆
    • Organizer
      日本生化学会大会シンポジウム
    • Place of Presentation
      京都国際会議場(招待講演)
    • Year and Date
      2011-09-21
    • Related Report
      2011 Annual Research Report
  • [Presentation] タンパク質架橋化酵素の高反応性基質配列の探索と活用2011

    • Author(s)
      伊藤みほ、福井美奈、鞍本克真、清水由隆、人見清隆
    • Organizer
      動物細胞工学会
    • Place of Presentation
      東京大学山上会館
    • Year and Date
      2011-07-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] Characterization of medaka transglutaminases, a protein cross-linking enzyme family2011

    • Author(s)
      斉藤 麻衣, 伊藤 みほ, 人見 清隆
    • Organizer
      Medaka Strategic Research
    • Place of Presentation
      Okazaki Conference Center, Aichi(岡崎市)
    • Related Report
      2013 Final Research Report
  • [Remarks] 自らの研究室において公表の基質・発現データベースのホームページを作成している

    • URL

      http://www.ps.nagoya-u.ac.jp/lab_pages/biochemistry/transglutaminases_database.html

    • Related Report
      2013 Final Research Report
  • [Remarks] トランスグルタミナーゼの網羅的な基質(発現)データベース

    • URL

      http://www.ps.nagoya-u.ac.jp/lab_pages/biochemistry/transglutaminases_database.html

    • Related Report
      2013 Annual Research Report

URL: 

Published: 2011-04-06   Modified: 2019-07-29  

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