Analysis of regulatory mechanism of PI3K-Akt signaling pathway by TTC3

• Project/Area Number: 22770118
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Functional biochemistry
• Research Institution: Hokkaido University
• Principal Investigator: SUIDU Futoshi 北海道大学, 遺伝子病制御研究所, 講師 (90431379)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: タンパク分解 / リン酸化 / AKT / ユビキチン / セリンスレオニンキナーゼ / ダウン症 / 21Trisomy / TTC3 / タンパク質分解 / Akt / 21トリソミー / ２１トリソミー

Research Abstract

In order to elucidate the biological function of TTC3, which we previously identified as a novel ubiquitin ligase of Akt kinase, we analyzed an effect of ectopic expression of TTC3 into HEK 293T cells. Overexpression of TTC3 into 293T cells resulted in reduction of cell growth rate. Conversely, induction of siRNA of TTC3 into HT1080 caused acceleration of cell growth, meaning that TTC3 function as negative regulator of cell growth by inhibiting of Akt activity. By using 21 trisomy Down syndrome-derived cell lines, which TTC3 protein is spontaneously overexpressed, TTC3 knock down by siRNA induced enhancement of Akt activity. Collectively, TTC3 may function as a cell growth regulatorby modulating PI3K-Akt pathway in mammalian cells.

Research Products

• [Journal Article] Regulation of Akt by phosphorylation of distinct threonine and serine residues Threonine:Structure, Biosynthesis and Functions (2011)
  • Author(s): M.Noguchi＆F.Suizu
  • Journal Title: Advances in Medicine and Biology.47 Volume: 47 Pages: 165-171
• [Journal Article] Characterization of the interaction of Influenza virus NS1 with Akt. (2010)
  • Author(s): M. Matsuda, F.Suizu, N.Hirata ,T.Miyazaki,C.Obuse,M.Noguchi
  • Journal Title: Biochem Biophys Res Communic. Volume: 395 Pages: 312-317
  • NAID: 120002191111
  • Peer Reviewed
• [Presentation] Protooncogene TCL1b functions as an AKT kinase co-activator that exhibits oncogenic potency in vivo. (2012)
  • Author(s): Manabu Hashimoto, Mami Matsuda Futoshi Suizu,Tadashi Nagamine,Noriyuki Hirata, Hiroko Noguchi,Sinya Tanaka,Wataru Tokuyama,Masayuki Noguchi
  • Organizer: 第71回日本癌学会学術集会
  • Place of Presentation: 札幌市・ロイトン札幌
• [Presentation] Modulation of the Aktsignal by its binding proteins. (2012)
  • Author(s): 野口昌幸、水津太
  • Organizer: 第35回分子生物学会
  • Place of Presentation: 福岡市・福岡国際会議場
• [Presentation] Protooncogene TCL1b Functions as An Akt KinaseCo-activator that Exhibits On cogenicPotency In Vivo. (2012)
  • Author(s): Manabu Hashimoto,Futoshi Suizu,Wataru Tokuyama,Hiroko Noguchi,Mami Matsuda,Noriyuki Hirata,Tadashi Nagamine,Shinya Tanaka,Masayuki Noguchi
  • Organizer: 第35回分子生物学会
  • Place of Presentation: 福岡市・福岡国際会議場
• [Presentation] Protooncogene TCL1b functions as an AKT kinase co-activator that exhibits oncogenic potency in vivo. (2012)
  • Author(s): 橋本 学
  • Organizer: Mechanisms ＆Models of Cancer.
  • Place of Presentation: Cold Spring Harbor Laboratory(アメリカ）
• [Presentation] Protooncogene TCL1b functions as an AKT kinase co-activator that exhibits oncogenic potency in vivo (2012)
  • Author(s): 橋本 学
  • Organizer: 第７１回日本癌学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道）
• [Presentation] Akt結合因子による細胞反応性の修飾の分子機構 (2012)
  • Author(s): 野口昌幸
  • Organizer: 第35回分子生物学会
  • Place of Presentation: 福岡国際会議場（福岡県）
• [Presentation] Protooncogene TCL1b Functions as An Akt Kinase Co-activator that Exhibits On cogenic Potency In Vivo. (2012)
  • Author(s): 橋本 学
  • Organizer: 第35回分子生物学会
  • Place of Presentation: 福岡国際会議場(福岡県）
• [Presentation] Akt regulation by ubiquitin-proteasome pathways. (2011)
  • Author(s): F.Suizu
  • Organizer: AACR Special Conference
  • Place of Presentation: Hyatt Regency(サンフランシスコ・米)
  • Year and Date: 2011-02-26
• [Presentation] Characterization of the interaction of Akt with virus NS1 (2011)
  • Author(s): M. Matsuda, Suizu F, Hirata N, Miyazaki T, Obuse C, Noguchi M
  • Organizer: Keystone Symposia
  • Place of Presentation: Keystone Resort(コロラド・米)
• [Presentation] Characterization of the interaction of influenza virus NS1 with Akt. (2011)
  • Author(s): M. Matsuda,Futoshi Suizu,Noriyuki Hirata,Tadaaki Miyazaki,Chikashi Obuse, M.Noguchi
  • Organizer: 国際微生物学連合2011会議
  • Place of Presentation: 札幌市・札幌コンベンションセンター
• [Presentation] プロトオンコジーンTCL1bの生物機能解析 (2011)
  • Author(s): M.Hashimoto, F.Suizu, M.Matsuda, N.Hirata, M.Noguchi
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋・名古屋国際会議場
• [Presentation] プロトオンコジンTCL1bのAKT活性化補助因子としての役割について (2011)
  • Author(s): M.Hashimoto, F. Suizu,M. Matsuda, N.Hirata, M. Noguchi
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜市・パシフィコ横浜
• [Presentation] Characterization of protooncogene TCL 1b as an Akt kinase co-activator (2011)
  • Author(s): M.Noguchi
  • Organizer: CSHL Meeting
  • Place of Presentation: Cold Spring Harbor Laboratory（ｱﾒﾘｶ）
• [Presentation] Characterization of the interaction of influenza virus NS1 with Akt (2011)
  • Author(s): M. Matsuda
  • Organizer: 国際微生物学連合2011会議
  • Place of Presentation: 札幌ｺﾝﾍﾞﾝｼｮﾝｾﾝﾀｰ（北海道）
• [Presentation] プロトオンコジーンTCL1ｂの生物機能解析 (2011)
  • Author(s): 橋本 学
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県）
• [Presentation] プロトオンコジンTCL1ｂのAKT活性化補助因子としての役割について (2011)
  • Author(s): 橋本 学
  • Organizer: 第34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）
• [Presentation] ユビキチン化によるAKT活性の調節メカニズムの解析 (2010)
  • Author(s): 水津太
  • Organizer: 第33回 日本分子生物学会
  • Place of Presentation: 神戸ポートアイランド・神戸市
  • Year and Date: 2010-12-10
• [Presentation] Characterization of the interaction of influenza virus NS1 with Akt (2010)
  • Author(s): 松田真実
  • Organizer: 第33回 日本分子生物学会
  • Place of Presentation: 神戸ポートアイランド・神戸市
  • Year and Date: 2010-12-10
• [Presentation] ユビキチン化によるAKTの活性化制御の仕組み (2010)
  • Author(s): 野口昌幸
  • Organizer: 第69回 日本癌学会学術総会
  • Place of Presentation: リーガロイヤルホテル大阪・大阪市
  • Year and Date: 2010-09-24
• [Presentation] TTCによるAkt活性調節機構の解析 (2010)
  • Author(s): 水津太
  • Organizer: 第69回 日本癌学会学術総会
  • Place of Presentation: リーガロイヤルホテル大阪・大阪市
  • Year and Date: 2010-09-23
• [Presentation] TTCによるAkt活性調節機構の解析 (2010)
  • Author(s): 水津太
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪市・大阪国際会議場
• [Presentation] ユビキチン化によるAKT活性の調節メカニズムの解析 (2010)
  • Author(s): Futoshi Suizu,Yosuke Hiramuki,Fumihiko Okumura,Mami Matsuda,Akiko Okumura,Noriyuki Hirata,Masumi Narita,Takashi Kohono,Jun Yokota,Miyuki Bohgaki,Chikashi Obuse,Shigetsugu HatakeyamaToshiyuki Obata,Masayuki Noguchi
  • Organizer: 第33回日本分子生物学会
  • Place of Presentation: 神戸市・神戸ポートアイランド
• [Presentation] Characterization of the interaction of influenza virus NS1 with Akt (2010)
  • Author(s): Mami Matsuda, Futoshi Suizu, Noriyuki Hirata,Tadaaki Miyazaki,Chikashi Obuse,Masayuki Noguchi
  • Organizer: 第33回日本分子生物学会
  • Place of Presentation: 神戸市・神戸ポートアイランド
• [Book] Regulation of Akt by phosphorylation of distinct threonine and serine residues Threonine:Structure, Biosynthesis and Functions; (2011)
  • Author(s): M. Noguchi & F. Suizu.
  • Publisher: Advances in Medicine and Biology.47 Nova Science Publishers