The role of HBP23 to chronic myelogenous keukemia

HBP23在慢性粒细胞白血病中的作用

• 批准号: 14570132
• 负责人: ABE Yasuko
• 金额: $ 2.24万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570132/
• 关键词: rat; peroxiredoxin; HBP23; c-Abl; チオレドキシン; c-Abl tyrosine kinase

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.

HBP23，血红素结合蛋白23，是2-Cys过氧化物还氧蛋白家族的成员，具有过氧化物酶活性。晶体结构表明，Cys52与另一个亚基Cys173在氧化态下通过c端尾部交换形成分子间二硫化物，被几个疏水残基包围，活性位点{S中有保守的Arg128和Arg151。张广津等（1999）中华民国学报。96年,12333 - 12338}。在这项工作中，我们研究了HBP23与过氧化物酶活性和非受体酪氨酸激酶c-Abl之间的关系。HBP23和通过定点诱变制备的变异。所有蛋白均在大肠杆菌中过表达。非受体酪氨酸激酶c-Abl在杆状病毒-昆虫细胞系统中过表达。尺寸排除色谱分析表明，HBP23的四元结构交换范围从十聚体到二聚体，取决于氧化还原和蛋白质浓度/离子强度。采用硫氧还蛋白体系和DTT体系测定过氧化物酶活性。Cys52是被过氧化物氧化的位点。对于复合物的形成，硫氧还蛋白需要HBP23的Cys173。Cys52的反应性需要Arg128和Arg151。HBP23形成非受体酪氨酸激酶，类似于人类的同源物。

项目成果

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.

肌萎缩侧索硬化症 (ASL) 运动神经元中氧化还原系统的表达：对散发性 ALS、超氧化物歧化酶 1 (SOD-1) 突变家族性 ALS 和 SOD 突变 ALS 动物模型的免疫组织化学研究。

• 期刊: Acta Neuropathol. (in press)
• 作者: Kato;S.
• 通讯作者: S.

Unique amino acids cluster for switching from thedehydrogenase to oxidase form of xanthine oxidoreductanse.

独特的氨基酸簇，用于从黄嘌呤氧化还原酶的脱氢酶转换为氧化酶形式。

• 发表时间: 2003
• 期刊: Proc.Natl.Acad.Sci.USA. 100
• 作者: Kuwabara;Y.
• 通讯作者: Y.

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.

肌萎缩侧索硬化症 (ASL) 运动神经元中氧化还原系统的表达：对散发性 ALS、超氧化物歧化酶 1 (SOD-1) 突变家族性 ALS 和 SOD-1 突变 ALS 动物模型的免疫组织化学研究。

• 期刊: Acta Neuropathol. (in press)
• 作者: Kato;S.;Kato;M.;Abe;Y.;Matsumura;T.;Nishino;T.;Aoki;M.;Itoyame;Y.;Asayame;K.;Awaya;A.;Hirano;A.;Ohama;E.
• 通讯作者: E.

Kuwabara, Y.: "Unique amino acids cluster for switching from the dehydrogenase to oxidase form of xanthine oxidoreductase."Proc.Natl.Acad.Sci.USA.. 100. 8170-8175 (2003)

Kuwabara, Y.：“用于从黄嘌呤氧化还原酶的脱氢酶转换为氧化酶形式的独特氨基酸簇。”Proc.Natl.Acad.Sci.USA.. 100. 8170-8175 (2003)