Regulatory Mechanism for the reactive oxygen-producing enzyme family Nox

活性氧产生酶家族Nox的调控机制

• 批准号: 18390090
• 负责人: SUMIMOTO Hideki
• 金额: $ 10.7万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390090/
• 关键词: reactive oxygen species; protein; signal transduction; enzyme; NADPH oxidase; 活性酸素; シグナル云達; NADPHオキシダー; NAPDHオキシダーゼ

On the mechanism of the reactive oxygen-producing enzyme family Nox (NADPH oxidase), we obtained the following results during the course of this project. (1) We showed that an intramolecular interaction between the PX and PB1 domains of p40pax, a protein involved in Nox2 activation, regulates translocation of this protein to the phagosomal membrane, and also determined the crystal structure of the full-length p40phax. (2) We identified Nox2 regions, which participate in electron transfer in Nox2 and Nox2 binding to p22phax. (3) We demonstrated that Noxo1, an essential activator of Nox1, is kept in an inactive form via an intramolecular interaction, which is released by posttranslational modifications. (4) We clarified that the small GTPase Rac functions as an activator of Nox1 and Nox3 by interacting with Noxa1 and p67phax., respectively. (5) We also showed that Rac3 is capable of acting as a regulator of Nox1, Nox2, and Nox3, and that none of the activations of Nox1-3 by Rac1-3 requires the insert helix, a region specific to the Rho-family GTPases including Rac.

关于活性氧生成酶家族Nox （NADPH氧化酶）的机理，我们在本项目中获得了以下结果：(1)我们发现参与Nox2活化的蛋白p40pax的PX和PB1结构域之间的分子内相互作用调节了该蛋白向吞噬体膜的易位，并决定了全长p40pax的晶体结构。(2)我们发现了Nox2区域，它参与了Nox2与p22phax结合过程中的电子转移。(3)我们证明了Noxo1是Nox1的重要激活剂，通过分子内相互作用保持非活性形式，并通过翻译后修饰释放。(4)我们明确了小GTPase Rac通过与Noxa1和p67phax相互作用，作为Nox1和Nox3的激活剂。,分别。(5)我们还发现Rac3能够作为Nox1、Nox2和Nox3的调节因子，并且Rac1-3对Nox1-3的激活都不需要插入螺旋，插入螺旋是包括Rac在内的rho家族GTPases特有的区域。

项目成果

Expression and function of Noxolγ,an alternative splicing form of the NADPH oxidase organizer 1

NADPH 氧化酶组织者 1 的另一种剪接形式 Noxolγ 的表达和功能

• 发表时间: 2006
• 期刊: FEBS J. 273
• 作者: Takeya;R.;Taura;M.;Yamasaki;T.;Naito;S.;and Sumimoto;H.
• 通讯作者: H.

Increased expression of gp91^<phox> homologues of NAD(P)H oxidase in the aortic media during chronic hypertension;involvement of the rennin-angiotensin system

慢性高血压期间主动脉中层 NAD(P)H 氧化酶 gp91^<phox> 同源物的表达增加；肾素-血管紧张素系统的参与

• 发表时间: 2006
• 期刊: EMBO J. 25
• 作者: Onohara;N.;Nishida;M.;Inoue;R.;Kobayashi;H.;Sumimoto;H.;Sato;Y.;Mori;Y.;Nagao;T.;and Kurose;H.
• 通讯作者: H.

Molecular composition and regulation of Noxl-3.(invited speaker)

Noxl-3的分子组成及调控。（特邀报告人）

• 发表时间: 2006
• 作者: Zhang B;Une Y;Ge F;Fu X;Qian J;Zhang P;Sawashita J;Higuchi K;Mori M.;Hideki Sumimoto
• 通讯作者: Hideki Sumimoto

生体防御医学辞典

生物防御医学词典

• 发表时间: 2007
• 作者: 川上佳紀;竹本恵子;久本雅嗣;奥田徹;樋口京一;前田秀一郎;住本 英樹(共著者・共著者)
• 通讯作者: 住本 英樹(共著者・共著者)

Interaction between the SH3 domains and C-terminal proline-rich region in NADPH oxidase organizer1 (Noxol).

NADPH 氧化酶组织者 1 (Noxol) 中 SH3 结构域和 C 端富含脯氨酸区域之间的相互作用。

• 发表时间: 2007
• 期刊: Biochem.Biophys.Res.Commun. 352
• 作者: Yamamoto;A.;Kami;K.;Takeya;R.;and sumimoto;H.
• 通讯作者: H.