Preparation for PTD-Pin1 and its appllication to stem cell differentiation

• Project/Area Number: 26660287
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Applied molecular and cellular biology
• Research Institution: Tohoku University
• Principal Investigator: Uchida Takafumi 東北大学, 農学研究科, 教授 (80312239)
• Co-Investigator(Kenkyū-buntansha): 内田 千代子 福島大学, 人間発達文化学類, 教授 (80312776)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: Pin1 / 間葉系幹細胞 / 細胞分化 / 細胞膜透過性Pin1 / TAT-Pin1 / 脂肪細胞 / インテグリン / 酵素 / 分化 / 細胞周期 / 細胞膜透過 / 細胞死

Outline of Final Research Achievements

We prepared for (RGD)2-TAT-Pin1 as an novel Protein transduction domain (PTD)-Pin1 consisting of 2 of Arg-Gly-Asp（RGD）motif that binds to the integrin α5β1 expressing on mesenchymal stem cell membranes at the N-terminal end, trans-activator of transcription (TAT）and Pin1. Function of Pin1 was evaluated with the Pin1-knockout ASC clone prepared from the Pin1-/-；p53-/- mouse. The differentiation of ASCs into adipocytes was significantly improved by (RGD)2-TAT-Pin1. The effect of (RGD)2-TAT-Pin1 on differeantiation of ASC into osteoblasts and chondrocytes are being studied.

Research Products

• [Journal Article] Loss of Pin1 suppresses Hedgehog-driven medulloblastoma tumorigenesis. (2017)
  • Author(s): Xu T, Zhang H, Park S, Venneti S, Kuick R, Ha K, Michael LE, Santi M, Uchida C, Uchida T, Srinivasan A, Dlugosz A, Olson J, Camelo-Piragua S, Rual JF
  • Journal Title: Neoplasisa Volume: 19 Pages: 216-225
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Brown Algae polyphenol, a prolyl isomerase Pin1 inhibitor, prevents obesity by inhibiting the differentiation of stem cells into adipocytes. (2016)
  • Author(s): Suzuki A, Saeki T, Ikuji H, Uchida C, Uchida T
  • Journal Title: Plos One Volume: 11(12) Issue: 12 Pages: e0168830-e0168830
  • DOI: 10.1371/journal.pone.0168830
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The Protein Level and Transcription Activity of Activating Transcription Factor 1 is Regulated by Prolyl-isomerase Pin1 in Nasopharyngeal Carcinoma Progression. (2016)
  • Author(s): Huang GL, Liao D, Chen H, Lu Y, Chen L, Li H, Li B, Liu W, Ye C, Li T, Zhu Z, Wang J, Uchida T, Zou Y, Don Z, He Z
  • Journal Title: Cell Death Dis Volume: 7(12) Issue: 12 Pages: e2571-e2571
  • DOI: 10.1038/cddis.2016.349
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prolyl Isomerase Pin1 Regulates Doxorubicin- Inducible P-glycoprotein Level by Reducing Foxo3 Stability. (2016)
  • Author(s): Shimizu T, Bamba Y, Kawabe Y , Fukuda T, Fujimori F, Takahashi K, Uchida C, and Uchida T
  • Journal Title: Biochemical Biophysical Research Communications Volume: 471 Issue: 2 Pages: 328-333
  • DOI: 10.1016/j.bbrc.2016.02.014
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] sNOOOpy, a Sensor for Physiological NO3－/NO2－ Employing a Bacterial Two-Component Regulatory System. (2016)
  • Author(s): Hidaka M, Gotoh A, Shimizu T, Minamisawa K, Imamura H and Uchida T
  • Journal Title: Journal Biological Chemistry Volume: 291 Issue: 5 Pages: 2260-2269
  • DOI: 10.1074/jbc.m115.687632
  • Peer Reviewed
• [Journal Article] Mycoplasma pneumonia of swine (MPS) resistance and immune characteristics of pig lines generated by crossing an MPS pulmonary lesion selected Landrace line and a highly immune capacity selected Large White line. (2016)
  • Author(s): Borjigin L, Shimazu T, Katayama Y, Watanabe K, Kitazawa H, Roh SG, Aso H, Katoh K, Uchida T, Suda Y, Sakuma A, Nakajo M, Suzuki K
  • Journal Title: Animal Science Journal Volume: 印刷中 Issue: 8 Pages: 972-981
  • DOI: 10.1111/asj.12529
  • Peer Reviewed / Open Access
• [Journal Article] Immunogenic properties of Landrace pigs selected for resistance to mycoplasma pneumonia of swine. (2016)
  • Author(s): Borjigin L, Shimazu T, Katayama Y, Watanabe K, Kitazawa H, Roh S, Aso H, Katoh K, Uchida T, Suda Y, Sakuma A, Nakajo M and Suzuki K
  • Journal Title: Animal Science Journal Volume: 印刷中 Issue: 5 Pages: 638-645
  • DOI: 10.1111/asj.12471
  • Peer Reviewed / Open Access
• [Journal Article] Immunogenic properties of Landrace pigs selected for resistance to mycoplasma pneumonia of swine. (2016)
  • Author(s): Borjigin L, Shimazu T, Katayama Y, Li M, Satoh T, Watanabe K, Kitazawa H, Roh S, Aso H, Katoh K, Uchida T, Suda Y, Sakuma A, Nakajo M and Suzuki K
  • Journal Title: Animal Science Journal Volume: 印刷中 Issue: 3 Pages: 321-329
  • DOI: 10.1111/asj.12440
  • Peer Reviewed / Open Access
• [Journal Article] Prolyl isomerase Pin1 negatively regulates AMP-activated protein kinase (AMPK) by associating with the CBS domain in the γ subunit (2015)
  • Author(s): Nakatsu Y, Iwashita M, Sakoda H, Ono H, Nagata K, Matsunaga Y, Fukushima T, Fujishiro M, Kushiyama A, Kamata H, Takahashi S, Katagiri H, Honda H, Kiyonari H, Uchida T, Asano T
  • Journal Title: J Biol Chem Volume: 290 Issue: 40 Pages: 24255-24266
  • DOI: 10.1074/jbc.m115.658559
  • Peer Reviewed / Open Access
• [Journal Article] Pin1 Promotes Neuronal Death in Stroke by Stabilizing Notch Intracellular Domain (2015)
  • Author(s): 1.Baik SH, Fane M, Hyung PJ, Cheng YL, Yun UJ, Choi Y, Park JS, Chai B, Park JS, Back aik SH, Fane M, Hyung PJ, Cheng YL, Yun UJ, Choi Y, Park JS, Chai B, Park JS, Back SH, Jeong JI, Jang YJ, Bahn G, Lee JY, Li YI, Sobey C, Uchida T, Park JH, Kim HT, Tang S, Arumugam T and Jo DG.
  • Journal Title: Ann Neurol Volume: 77(3) Issue: 3 Pages: 504-516
  • DOI: 10.1002/ana.24347
  • Peer Reviewed / Open Access
• [Journal Article] Phosphatidylethanolamine plasmalogen enhances the inhibiting effect of phosphatidylethanolamine on γ-secretase activity (2015)
  • Author(s): Tomoko Onodera, Eugene Futai, Eiichiro Kan, Naoki Abe, Takafumi Uchida, Yoshiyuki Kamio and Jun Kaneko
  • Journal Title: Journal of Biochemistry,156,(2015)] Volume: 156 Issue: 5 Pages: 301-309
  • DOI: 10.1093/jb/mvu074
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Neurotensin enhances sperm capacitation and the acrosome reaction in mice. (2014)
  • Author(s): 佐藤英明
  • Journal Title: BIOLOGY OF REPRODUCTION Volume: 91(2)53 Issue: 2 Pages: 1-9
  • DOI: 10.1095/biolreprod.113.112789
  • Peer Reviewed / Open Access
• [Journal Article] The nitrate-sensing NasST system regulates nitrous oxide reductase and periplasmic nitrate reductase in Bradyrhizobium japonicum. (2014)
  • Author(s): Sanchez, C., M. Itakura, T. Okubo, T. Matsumoto, H. Yoshikawa, A. Gotoh, M. Hidaka, T. Uchida, and K. Minamisawa.
  • Journal Title: Environmental Microbiology Volume: 16 Issue: 10 Pages: 3263-3274
  • DOI: 10.1111/1462-2920.12546
  • Peer Reviewed / Open Access
• [Journal Article] Pin1 regulates osteoclast fusion through suppression of the master regulator of cell fusion DC-STAMP. (2014)
  • Author(s): 5.Islam R, Bae HS, Yoon WJ, Woo KM, Baek JH, Kim HH, Uchida T, and Ryoo HM
  • Journal Title: J Cell Physiol, Volume: 229 Issue: 12 Pages: 2166-2174
  • DOI: 10.1002/jcp.24679
  • Peer Reviewed / Open Access
• [Journal Article] A high-throughput screen for inhibitors of the prolyl isomerase, Pin1, identifies a seaweed polyphenol that reduces adipose cell differentiation. (2014)
  • Author(s): Mori T, Hidaka M, Ikuji H, Yoshizawa I, Toyohara H, Okuda T, Uchida C, Asano T, Yotsu-Yamashita M, Uchida T
  • Journal Title: Biosci. Biotechnol. Biochem. Volume: 78 Issue: 5 Pages: 832-838
  • DOI: 10.1080/09168451.2014.905189
  • Peer Reviewed / Open Access
• [Journal Article] Site-specific Phosphorylation of Tau Protein is Associated with Deacetylation of Microtubules in Mouse Spermatogenic Cells During Meiosis. (2014)
  • Author(s): 7.Inoue H, Hiradate Y, Shirakata Y, Kanai K, Kosaka K, Gotoh A, Fukuda Y, Nakai Y, Uchida T, Sato E and Tanemura K
  • Journal Title: FEBS Lett. Volume: 588, Issue: 11 Pages: 2003-2008
  • DOI: 10.1016/j.febslet.2014.04.021
  • Peer Reviewed / Open Access
• [Presentation] Establishment of mesenchymal stem cell line from p53-deleted mouse and its application to drug discovery (2017)
  • Author(s): Uchida T, Miyashita T, Suzuki T, Suzuki A, Uchida C
  • Organizer: Bioprocessing summit
  • Place of Presentation: Boston, USA
  • Year and Date: 2017-08-16
  • Int'l Joint Research
• [Presentation] Pin1によるFoxO3を介したP-glycoproteinの発現制御機構 (2017)
  • Author(s): 清水泰希、坂場義正、川邉庸介、内田隆史
  • Organizer: 日本農芸化学会
  • Place of Presentation: 京都女子大学（京都府・京都市）
  • Year and Date: 2017-03-19
• [Presentation] Pin1は脂肪由来間葉系幹細胞の分化を促進させた (2016)
  • Author(s): 鈴木寿弥 等
  • Organizer: 日本分子生物学会年会、日本生化学会大会 合同大会
  • Place of Presentation: 神戸ポートアイランド(兵庫県 神戸市）
  • Year and Date: 2016-12-03
• [Presentation] プロリン異性化酵素Pin1は受精卵の卵割に機能する (2016)
  • Author(s): 星野由美、宮本拓真、川合智子、内田隆史、島田昌之
  • Organizer: 第38回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2016-12-02
• [Presentation] 海藻ポリフェノールはPin1活性を阻害しマウスの脂肪量を低下させた (2016)
  • Author(s): 鈴木充子 等
  • Organizer: 日本分子生物学会年会、日本生化学会大会 合同大会
  • Place of Presentation: 神戸ポートアイランド(兵庫県 神戸市）
  • Year and Date: 2016-12-02
• [Presentation] Growth arrest specific protein 7bによる微小管関連蛋白質Tauの制御 (2016)
  • Author(s): 清水泰希、藤田彩子、後藤愛那、日高將文、内田隆史
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際会議センター （宮城県・仙台市）
  • Year and Date: 2016-09-25
• [Presentation] Pin1はCamKIIの活性を低下させることでTauの機能制御を行う (2016)
  • Author(s): 菅原佑衣、金井研太、清水泰希、広瀬恵子、日高将文、内田千代子、内田隆史
  • Organizer: 第89回本生化学会大会
  • Place of Presentation: 仙台国際会議センター （宮城県・仙台市）
  • Year and Date: 2016-09-25
• [Presentation] プロリン異性化酵素Pin1阻害剤である褐藻ポリフェノールによる脂肪由来間葉系幹細胞の脂肪細胞への分化抑制 (2016)
  • Author(s): 鈴木充子、佐伯俊之、内田隆史、内田千代子
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際会議センター （宮城県・仙台市）
  • Year and Date: 2016-09-25
• [Presentation] c-Mycとの相互作用によるPin1の構造変化を解析できるFRET法の確立 (2016)
  • Author(s): 畠山皓大, 岡部恵美子、日高将文、内田隆史
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際会議センター （宮城県・仙台市）
  • Year and Date: 2016-09-25
• [Presentation] プロリン異性化酵素Pin1による着床前初期胚発生に果たす役割 (2016)
  • Author(s): 星野由美、川合智子、内田隆史、島田昌之
  • Organizer: 第34回日本受精着床学会総会・学術講演会
  • Place of Presentation: 軽井沢プリンスホテルウエスト（長野県・軽井沢町）
  • Year and Date: 2016-09-15
• [Presentation] 卵子の形成・成熟、受精後の初期胚発生過程におけるプロリン異性化酵素Pin1の発現と機能 (2016)
  • Author(s): 星野由美、川合智子、内田隆史、島田昌之
  • Organizer: 第57回日本卵子学会
  • Place of Presentation: 新潟コンベンションセンター（新潟県・新潟市）
  • Year and Date: 2016-05-14
• [Presentation] プロリン異性化酵素Pin1阻害ポリフェノールの発見 (2016)
  • Author(s): 對馬早織 等
  • Organizer: 日本農芸化学会
  • Place of Presentation: 札幌コンベンションセンター（北海道 札幌市）
  • Year and Date: 2016-03-30
• [Presentation] 微生物環境応答システムの速度論的解析と応用開発 (2016)
  • Author(s): 日高將文 等
  • Organizer: 日本農芸化学会
  • Place of Presentation: 札幌コンベンションセンター（北海道 札幌市）
  • Year and Date: 2016-03-30
• [Presentation] Crisper/Cas9 法によるPin1-欠損ヒト細胞の作製と解析 (2016)
  • Author(s): 秋吉皓太 等
  • Organizer: 日本農芸化学会
  • Place of Presentation: 札幌コンベンションセンター（北海道 札幌市）
  • Year and Date: 2016-03-29
• [Presentation] マウス卵子および初期胚におけるPin1の局在解析 (2015)
  • Author(s): 高橋さゆり 等
  • Organizer: 日本卵子学会
  • Place of Presentation: 栃木県総合文化センター（栃木県 宇都宮市）
  • Year and Date: 2015-05-31
• [Presentation] Pin1によるタウキナーゼ活性制御の解析 (2015)
  • Author(s): 馬場 貴大, 金井 研太, 日高 將文, 内田 隆史
  • Organizer: 農芸化学会
  • Place of Presentation: 岡山大学
  • Year and Date: 2015-03-27
• [Presentation] Pin1 gene deficient mice impaired spatial cognitive function and exhibited frontotemporal lobar atrophy (2015)
  • Author(s): 大滝博和、桐山恵介、渡邊潤、山本麗奈、松本皆子、高橋勝彦、内田隆史、塩田清二
  • Organizer: 日本解剖学会総会・全国学術集会・日本生理学会大会合同大会（
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2015-03-21
• [Presentation] 根粒菌の二成分制御システムを利用したNO3－/NO2－バイオセンサーの開発 (2014)
  • Author(s): 後藤愛那、日高將文、清水泰希、板倉学、クリスチーナ・サンチェス、南澤究、今村博臣、内田隆史
  • Organizer: 日本生化学会大会
  • Place of Presentation: 京都国際会館
  • Year and Date: 2014-10-15
• [Presentation] Improvement of FRET based indicator for structural change of Pin1 (2014)
  • Author(s): 岡部恵美子、日高將文、内田隆史
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: 横浜国際会議場
  • Year and Date: 2014-10-15
• [Presentation] プロリン異性化酵素Pin1による脳内CaMKIIの活性と安定性制御 (2014)
  • Author(s): 金井研太、馬場貴大、日高 將文、内田 隆史
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: 横浜国際会議場
  • Year and Date: 2014-10-15
• [Presentation] Pin1阻害剤としてのポリフェノール類の構造・機能相関 (2014)
  • Author(s): 小坂啓太、生地絋子、日高將文、内田隆史
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: 横浜国際会議場
  • Year and Date: 2014-10-15
• [Presentation] Pin1/p53ダブルノックアウトマウス由来 脂肪由来間葉系幹細胞株の樹立と解析 (2014)
  • Author(s): 佐伯俊幸、鈴木寿弥、秋吉皓太、阿部素子、内田隆史
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: 横浜国際会議場
  • Year and Date: 2014-10-15
• [Remarks] 東北大学農学研究科 分子酵素学研究室
  • URL: http://www.agri.tohoku.ac.jp/enzyme/index-j.html
• [Remarks] 分子酵素研究室
  • URL: http://www.agri.tohoku.ac.jp/enzyme/index-j.html