Analyses and applications of novel mechanism of phospho-independent regulation of lipid metabolism by Trypanosoma brucei 14-3-3

• Project/Area Number: 20590434
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Parasitology (including Sanitary zoology)
• Research Institution: Kurume University
• Principal Investigator: INOUE Masahiro Kurume University, 医学部, 教授 (00232562)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 脂質代謝 / 蛋白リン酸化酵素 / 結合蛋白 / ブルーストリパノソーマ / 2014 / 03 / 14-3-3タンパク / トリパノソーマ / 遊離脂肪酸 / トリグリセライド / リン酸化ペプチド / タンパク-タンパク相互作用 / 14-3-3 / 解糖系 / アフリカトリパノソーマ / Tb14-3-3 / Triglyceride / Free fatty acid / acetyl-CoA carboxylase / biotin-acetyl-CoA ligase / acetyl-CoA synthetase / Tb14-3-3ノックダウン昆虫型細胞株

Research Abstract

Trypanosoma brucei is a causative agent of sleeping sickness. More than 30,000 infected patients died of this devastating disease. One of the aims for this research is to identify the molecular mechanisms by which T. brucei 14-3-3s control the motility, cytokinesis, and cell cycle focusing on the lipid metabolism controlled by Tb14-3-3s as we discovered. We found that Tb14-3-3s interact with the enzymes involved in sugar or lipid metabolism, and protein kinases. One of the protein kinases among them is found out to be critical for the regulation of the motility, cytokinesis and cell cycle.

Research Products

• [Journal Article] Phosphorylation- Dependent Protein Interaction with Trypanosoma brucei 14-3-3 Proteins that Display Atypical Target Recognition. (2010)
  • Author(s): Inoue M., et al.
  • Journal Title: PLoS One 5(12)
  • Peer Reviewed
• [Journal Article] Epistatic and Functional Interactions of Catecho-O-Methyltransferase(COMT) and AKT1 on Neuregulin 1-ErbB Signaling in Cell Models. (2010)
  • Author(s): Sei Y., et al.
  • Journal Title: PLoS One 5(5)
  • Peer Reviewed
• [Journal Article] Phosphorylation-Dependent Protein Interaction with Trypanosoma brucei 14-3-3 Proteins that Display Atypical Target Recognition. (2010)
  • Author(s): M.Inoue, et al.
  • Journal Title: PLoS One Volume: 5(12)
  • Peer Reviewed
• [Journal Article] Epistatic and Functional Interactions of Catecho-O-Methyltransferase(CO MT) and AKT1 on Neuregulin 1-ErbB Signaling in Cell Models. (2010)
  • Author(s): Yoshitatsu Sei, et al.
  • Journal Title: PLoS One Volume: 5(5)
  • Peer Reviewed
• [Journal Article] A Critical Role for highly Conserved GLU610 Residue of Oligopeptidase B from Trypanosoma Brucei in Thermal Stability (2010)
  • Author(s): Nor Ismaliza Mohd Ismail, et al.
  • Journal Title: The Journal of Biochemistry 147 Pages: 201-211
  • Peer Reviewed
• [Journal Article] Phosphorylation-dependent Lys63-linked polyubiquitination of Daxx is essential for sustained TNF -{alpha}-induced ASK1 activation. (2009)
  • Author(s): Fukuyo Y., Kitamura T., Inoue M., Horikoshi NT, Higashikubo R, Hunt CR, Usheva A, Horikoshi N.
  • Journal Title: Cancer Res. 69(19) Pages: 7512-7517
  • Peer Reviewed
• [Journal Article] Mutant p53 disrupts the stress MAPK activation circuit induced by ASK1-dependent stabilization of Daxx. (2009)
  • Author(s): Kitamura T., Fukuyo Y., Inoue M., Horikoshi NT., Shindoh, M., Rogers BE., Usheva, A., Horikoshi, N.
  • Journal Title: Cancer Res. 69(19) Pages: 7681-7688
  • Peer Reviewed
• [Journal Article] A Critical Role for highly Conserved GLU610 Residue of Oligopeptidase B from Trypanosoma Brucei in Thermal Stability. (2009)
  • Author(s): Ismail NI., Yuasa T., Yuasa K., Nambu Y, Nisimoto M., Goto M., Matsuki H., Inoue M., Nagahama M., Tsuji A.
  • Journal Title: J.Biochem. 147(2) Pages: 201-211
  • NAID: 10027873746
  • Peer Reviewed
• [Journal Article] Mutant p53 disrupts the stress MAPK activation circuit induced by ASK1-denendent stabilization of Daxx (2009)
  • Author(s): Tetsuya Kitamura, et al.
  • Journal Title: Cancer Research 69 Pages: 7681-7688
  • Peer Reviewed
• [Journal Article] Phosphorylation-dependent Lys63-linked polyubiquitination of Daxx is essential for sustained TNF-α-induced ASK1 activation (2009)
  • Author(s): Yayoi Fukuyo, et al.
  • Journal Title: Cancer Research 69 Pages: 7512-7517
  • Peer Reviewed
• [Journal Article] Oxidative Stress Plays a Criticaal Role in Inactivating Mutant BRAF by Geldanamycin Derivatives. (2008)
  • Author(s): Y. Fukuyo, M. Inoue, T. Nakajima, et al.
  • Journal Title: Cancer Res 68 Pages: 6324-6330
  • Peer Reviewed
• [Presentation] 普遍的でない分子認識機構をもつトリパノソーマ14-3-3に結合するキナーゼの発見 (2010)
  • Author(s): 井上雅広
  • Organizer: 第9回分子寄生虫・マラリア研究フォーラム
  • Place of Presentation: 長崎大学坂本キャンパス(長崎市)
  • Year and Date: 2010-10-09
• [Presentation] Biological significance of heterodimeric form of Trypanosoma brucei 14-3-3I and II. (2009)
  • Author(s): 井上雅広、安田幸一、上村春樹、杉本佳織、井上大志、福間利英
  • Organizer: 第78回日本寄生虫学会大会
  • Place of Presentation: 東京
  • Year and Date: 2009-03-27
• [Presentation] Biological significance of heterodimeric form of Trypanosoma brucei 14-3-3 I and II (2009)
  • Author(s): 井上雅広, 他
  • Organizer: 第78回日本寄生虫学会大会
  • Place of Presentation: 法政大学(東京)
  • Year and Date: 2009-03-27
• [Presentation] Biological significance of heterodimeric form of Trypanosoma brucei 14-3-3I and II. (2009)
  • Author(s): 井上雅広
  • Organizer: 日米医学協力研究会 寄生虫疾患専門部会 第43回日米合同会議
  • Place of Presentation: 東京
  • Year and Date: 2009-01-08
• [Presentation] Biological significance of heterodimeric form of Trypanosoma brucei 14-3-3 I and II (2009)
  • Author(s): Masahiro Inoue
  • Organizer: 日米医学協力研究会 寄生虫疾患専門部会第43回日米合同会議
  • Place of Presentation: 国立医療センター(東京)
  • Year and Date: 2009-01-08
• [Presentation] 普遍的でない分子認識機構をもつトリパノソーマ14-3-3 に結合するキナーゼの発見 (2008)
  • Author(s): 井上雅広
  • Organizer: 第9回分子寄生虫・マラリア研究フォーラム
  • Place of Presentation: 長崎
  • Year and Date: 2008-10-09
• [Patent(Industrial Property Rights)] 原虫の増殖阻害剤を検出する方法 (2008)
  • Inventor(s): 井上雅広
  • Industrial Property Rights Holder: 井上雅広、上村春樹
  • Filing Date: 2008-10-08