Establishment of methods for prediction of the function of functionally-unknown gene products by the analysis of the posttranslational protein modifications.

• Project/Area Number: 15580080
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied biochemistry
• Research Institution: Yamaguchi University
• Principal Investigator: UTSUMI Toshihiko Yamaguchi University, Department of Biological Chemistry, Faculty of Agriculture, Professor, 農学部, 教授 (20168727)
• Project Period (FY): 2003 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,900,000); Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000); Fiscal Year 2003: ¥2,300,000 (Direct Cost: ¥2,300,000)
• Keywords: prediction / protein function / functionally-unknown protein / posttranslational modification / protein N-myristoylation / modification signal

Research Abstract

Upon the completion of the Human Genome Project, huge numbers of genetic sequences are now available. However, the function of many of these genes has not been identified. Therefore, the identification of the function of these genes is one of the most important purposes of the study of Proteomics.
Now, it is well known that many of the posttranslational modifications such as proteolytic processing, phosphorylation, glycosylation, lipid modifications, ADP-ribosylation etc. play critical roles in the structure and function of protein and regulate many cellular events such as intracellular signal transduction. However, systematic method to analyze the posttranslational modification of protein has not been established.
In the present study, we have shown that targeting, processing and modification of a distinct protein could be successfully detected by using metabolic labeling in an in vitro translation system or in transfected cells. Since many of these posttranslational modifications play specific roles in the structure and function of protein, it might be possible to predict the function of the protein from these experimental observations.

Research Products

• [Journal Article] N-terminus of B96Bom, a Bombyx mori G-protein-coupled receptor, is N-myristoylated and translocated across the membrane. (2005)
  • Author(s): Utsumi, T. et al.
  • Journal Title: FEBS Journal 272 Pages: 472-481
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] N-terminus of B96Bom, a Bombyx mori G-protein-coupled receptor, is N-myristoylated and translocated across the membrane. (2005)
  • Author(s): Utsumi, T., Ohta, H., Kayano, Y., Sakural, N., Ozoe, Y.
  • Journal Title: FEBS Journal 272 Pages: 472-481
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Vertical-scanning mutagenesis of amino acids in a model N-myristoylation motif reveals the major amino-terminal sequence requirements for protein N-myristoylation (2004)
  • Author(s): Utsumi, T. et al.
  • Journal Title: European Journal of Biochemistry 271 Pages: 863-874
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] N-ミリストイル化によるタンパク質の膜局在化と機能調節 (2004)
  • Author(s): 内海俊彦
  • Journal Title: 実験医学 22 Pages: 1252-1259
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Oxidative stress underlies the mechanism for Ca^<2+>- induced permeability transition of mitochondria. (2004)
  • Author(s): Kanno, T., Sato, E.F., Muranaka, S., Fujita, H., Utsumi, T., Inoue, M., Utsumi, K.
  • Journal Title: Free Rad.Res. 38 Pages: 27-35
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Vertical-scanning mutagenesis of amino acids in a model N-myristoylation motif reveals the major amino-terminal sequence requirements for protein N-myristoylation. (2004)
  • Author(s): Utsumi, T., Nakano, K., Funakoshi, T., Kayano, Y., Nakao, S., Sakurai, N., Iwata, H., Ishisaka, R.
  • Journal Title: Eur.J.Biochem. 271 Pages: 863-874
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification of amino acid residues interacting with tyramine in the Bombyx mori tyramine receptor. (2004)
  • Author(s): Ohta, H., Utsumi, T., Ozoe, Y.
  • Journal Title: Insect Molecular Biology 13 Pages: 531-538
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification of amino acid residues interacting with tyramine in the Bombyx mori tyramine receptor. (2004)
  • Author(s): Ohta, H. et al.
  • Journal Title: Insect Molecular Biology 13 Pages: 531-538
• [Journal Article] アクトネル(リセドロネート)によるU937細胞のアポトーシスとその機構 (2004)
  • Author(s): 藤田洋史 ら
  • Journal Title: 医学と薬学 51 Pages: 697-710
• [Journal Article] B96Bom encodes a Bomyx mori tyramine receptor negatively coupled to adenylate cyclase (2003)
  • Author(s): Ohta, H. et al.
  • Journal Title: Insect Molecular Biology 12 Pages: 217-223
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Topogenesis of two transmembrane type K^+ channels, Kir2.1 and KcsA (2003)
  • Author(s): Umigai, N. et al.
  • Journal Title: Journal of Biological Chemistry 278 Pages: 40373-40384
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] In vitro及びin vivo代謝標識法を用いた蛋白質翻訳後修飾の解析 (2003)
  • Author(s): 内海俊彦
  • Journal Title: 生化学 75 Pages: 373-378
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] B96Bom encodes a Bomyx mori tyramine receptor negatively coupled to adenylate cyclase. (2003)
  • Author(s): Ohta, H., Utsumi, T., Ozoe, Y.
  • Journal Title: Insect Molecular Biology 12 Pages: 217-223
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Mechanism of enhanced apoptosis in HL-60 cells by UV-irradiated n-3 and n-6 polyunsaturated fatty acids. (2003)
  • Author(s): Arita, K., Yamamoto, Y., Takehara, Y., Utsumi, T., Kanno, T., Miyaguchi, C., Akiyama, J., Yoshioka, T., Utsumi, K.
  • Journal Title: Free Radic.Biol.Med. 35 Pages: 189-199
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Topogenesis of two transmembrane type K^+ channels, Kir2.1 and KcsA. (2003)
  • Author(s): Umigai, N., Sato, Y., Mizutani, A., Utsumi, T., Sakaguchi, M., Uozumi, N.
  • Journal Title: J.Biol.Chem. 278 Pages: 40373-40384
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Involvement of Ras/Extracellular signal-regulated kinase, but not Akt pathway in risedronate-induced apoptosis of U937 cells and its suppression by cytochalasin B.
  • Author(s): Fujita, H., Utsumi, T., Muranaka, S., Ogino, T., Yano, H., Akiyama, J., Yasuda, T., Utsumi, K.
  • Journal Title: Biochem Pharmacol. (In press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Involvement of Ras/Extracellular signal-regulated kinase, but not Akt pathway in risedronate-induced apoptosis of U937 cells and its suppression by cytochalasin B.
  • Author(s): Fujita, H. et al.
  • Journal Title: Biochemical Pharmacology (印刷中)
• [Book] 「膜局在性のタンパク質工学的改変による生理活性タンパク質の機能変換」タンパク質工学 (2003)
  • Author(s): 内海俊彦 ら
  • Publisher: 医学書院
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ohta, H. et al.: "B96Bom encodes a Bomyx mori tyramine receptor negatively coupled to adenylate cyclase"Insect Molecular Biology. 12. 217-223 (2003)
• [Publications] Arita, K. et al.: "Mechanism of enhanced apoptosis in HL-60 cells by UV-irradiated n-3 and n-6 polyunsaturated fatty acids"Free Radic. Biol. Med.. 35. 189-199 (2003)
• [Publications] Umigai, N. et al.: "Topogenesis of two transmembrane type K^+ channels, Kir2.1 and KcsA"J. Biol. Chem.. 278. 40373-40384 (2003)
• [Publications] Kanno, T. et al.: "Oxidative stress underlies the mechanism for Ca^<2+>-induced permeability transition of mitochondria"Free Rad. Res.. 38. 27-35 (2004)
• [Publications] Utsumi, T. et al.: "Vertical-scanning mutagenesis of amino acids in a model N-myristoylation motif reveals the major amino-terminal sequence requirements for protein N-myristoylation"Eur.J.Biochem.. 271. 863-874 (2004)
• [Publications] 内海俊彦: "「膜局在性のタンパク質工学的改変による生理活性タンパク質の機能変換」タンパク質工学"医学書院. 165-204 (2003)