The role of HBP23 to chronic myelogenous keukemia

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 14570132
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Nippon Medical School
• Principal Investigator: ABE Yasuko Nippon Medical School, Dept.Mol.Biol., Lecturer, 医学部, 講師 (60089612)
• Co-Investigator(Kenkyū-buntansha): MATSUMURA Tomohiro Nippon Medical School, Dept.Mol.Biol., Assistant, 医学部, 助手 (20297930)
• Project Period (FY): 2002 – 2003
• Keywords: rat / peroxiredoxin / HBP23 / c-Abl

Research Abstract

HBP23, heme-binding protein 23, is a member of 2-Cys peroxiredoxin family, and exhibits a peroxidase activity. The crystal Structure shows that Cys52 forms the intermolecular disulfide with Cys173 from another subunit by C-terminal tail swapping in the oxidized form, being surrounded by several hydrophobic residues and the conserved Arg128 and Arg151 in the active site pocket {S.Hirotsu et al.(1999) Proc.Natl.Acad.Sd.U.S.A. 96, 12333-12338}. In this work, we studied the relationships between HBP23 and peroxidase activity, and non-receptor tyrosine kinase c-Abl. HBP23 and the variants prepared by using site-directed mutagenesis. All proteins were overexpressed in E.coli. Non-receptor tyrosine kinase c-Abl was overexpressed in baculovirus-insect cell system. Size-exclusion chromatographic analysis showed that the quaternary structure of HBP23 exchanged ranging from the decamer to the dimer, depending on redox and protein concentration/ionic strength. Peroxidase activity was measured by two systems, thioredoxin system and DTT system. Cys52 was the site for oxidation by peroxides. For the complex formation, thioredoxin required Cys173 of HBP23. Arg128 and Arg151 were required for the reactivity of Cys52. HBP23 formed non-receptor tyrosin kinase, like the human homologue.

Research Products

• [Journal Article] Unique amino acids cluster for switching from thedehydrogenase to oxidase form of xanthine oxidoreductanse. (2003)
  • Author(s): Kuwabara, Y.
  • Journal Title: Proc.Natl.Acad.Sci.USA. 100 Pages: 8170-8175
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Unique amino acids cluster for switching from the dehydrogenase to oxidase form of xanthine oxidoreductase. (2003)
  • Author(s): Kuwabara, Y., Nishino, T., Okamoto, K., Matsumura, T., Eger, B., Pal, E., Nishino, T.
  • Journal Title: Proc.Natl.Acad.Sci.USA 100 Pages: 8170-8175
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Redox system expression in the motor neurone in amyrotrophic lateral sclerosis(ASL) : Immunohistochemical studies on sporadic ALS,superoxide dismutase 1(SOD-1) mutated familial ALS,andSOD-Imutated ALS animal models.
  • Author(s): Kato, S.
  • Journal Title: Acta Neuropathol. (in press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Redox sysetm expression in the motor neurone in amyrotropic lateral sclerosis (ASL):Immunohistochemical studies on sporadic ALS, superoxide dismutase 1 (SOD-1)mutated familial ALS, and SOD-1mutated ALS animal models.
  • Author(s): Kato, S., Kato, M., Abe, Y., Matsumura, T., Nishino, T., Aoki, M., Itoyame, Y., Asayame, K., Awaya, A., Hirano, A., Ohama, E.
  • Journal Title: Acta Neuropathol. (in press)
  • Description: 「研究成果報告書概要(欧文)」より