Studies on proteolysis mediated by the proteasomes and ubiquitin

蛋白酶体和泛素介导的蛋白水解研究

• 批准号: 13002008
• 负责人: TANAKA Keiji
• 金额: $ 344.45万
• 依托单位: Tokyo Metropolitan Organization for Medical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Specially Promoted Research
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13002008/
• 关键词: enzyme; signal transduction; stress; protein; neurodegenerative diseases; proteasome; ubiquitin; 抗原プロセシング; PA28; ユビキチンリガーゼ; SCF; NEDD8; 品質管理; ユビキチン様蛋白質

The proteasome (a eukaryotic ATP-dependent protease complex) is a sophisticated cellular apparatus capable of shredding unnecessary proteins modified by ubiquitin (a posttranslational modifier serving a destination signal for proteolysis) selectively. It plays a central role in the control of a diverse array of cellular activities by catalyzing biological reactions rapidly, orderly, exhaustively, and uni-directionally. Over the past 25 years, we have been aiming to elucidate comprehensively the divergent roles of the ubiquitin-proteasome system (UPS) in the life science field. In the present project named "Studies on proteolysis mediated by the proteasomes and ubiquitin", our research projects on the proteasomes were (1) the analysis of the tertiary structure of the mammalian proteasome as a unusually large multi-protein complex, (2) the clarification of assembling mechanisms, focusing on the newly-discovered PAC (proteasome assembling chaperone) 1/2 heterodimeric complex and Hsp90, and (3) immunogenetic analysis of the new proteasome activator family proteins of PA28α, PA28β and PA28γ. In the ubiquitin project, we were interested in analyzing the quality-control ubiquitin-protein ligases (E3s) in cells: CHIP is a molecular chaperone-dependent E3, Parkin is encoded by the causative gene of eating of oneself") and two novel ubiquitin-like (UBL) modifying systems, such as NEDD8 and Ufml pathways, by generation of model mice with impairment of various related genes. Recently, various diseases, such as cancers, infectious diseases, and neurodegenerative diseases, have been increasing in the aged society of the 21st century. Considering such circumstances, it has been clarified, as a central scenario, that dysfunctioning of UPS causes these intractable diseases. Thus, our studies may contribute to the development of new bio-science field as well as to that of therapies for intractable diseases.

蛋白酶体（一种真核ATP依赖性蛋白质复合物）是一种精致的细胞设备，能够选择由泛素修饰的不必要的蛋白质（用于蛋白水解的目的地信号）修饰的不必要的蛋白质。它通过快速催化生物学反应，详尽的，详尽的和单向催化生物反应，在控制潜水的细胞活性中起着核心作用。在过去的25年中，我们的目标是完全阐明生命科学领域中泛素 - 蛋白酶体系统（UPS）的作用。 In the present project named "Studies on proteolysis mediated by the proteasomes and ubiquitin", our research projects on the proteasomes were (1) the analysis of the tertiary structure of the mammalian proteasome as a rarely large multi-protein complex, (2) the clarification of assembling mechanisms, focusing on the newly-discovered PAC (proteasome assembling chaperone) 1/2 heterodimeric complex and HSP90和（3）PA28α，PA28β和PA28γ的新蛋白质激活蛋白的免疫遗传学分析。在泛素项目中，我们有兴趣分析细胞中的质量控制泛素 - 蛋白质蛋白连接酶（E3S）：CHIP是一种分子链链依赖的E3，Parkin是由饮食的病原体编码的”，由两个新型泛素（UBL）修改系统（例如），例如Nekify System of Modile of Modile offify offient offient offient offient（UBL），例如Modile nodify System，例如NeD8和UFMLED 8和UFML，以及UFML的neD8和UFML，在各种相关的基因中，各种疾病（例如癌症，传染病和神经退行性疾病）在21世纪的老年社会中一直在增加。顽固的疾病。

项目成果

A novel protein-conjugating system for Ufm1, a ubiquitin-fold modifier

• DOI: 10.1038/sj.emboj.7600205
• 发表时间: 2004-05-05
• 期刊: EMBO JOURNAL
• 影响因子: 11.4
• 作者: Komatsu, M;Chiba, T;Tanaka, K
• 通讯作者: Tanaka, K

14-3-3h is a novel regulator of parkin ubiquitin-ligase

14-3-3h 是 Parkin 泛素连接酶的新型调节剂

• 发表时间: 2006
• 期刊: EMBOJ (In press)
• 作者: Sato S;Chiba;Tanaka K;T;Mizuno Y;Hattori N;et al.
• 通讯作者: et al.

The molecular chaperone Hsp90 interacts with 26S proteasomes and regulates their a ssembly

分子伴侣 Hsp90 与 26S 蛋白酶体相互作用并调节其组装

• 发表时间: 2003
• 期刊: EMBO J. 22
• 作者: Imai;J.;Maruya;M.;Yashiroda;H.;Yahara;I.;Tanaka;K.
• 通讯作者: K.

Parkin binds the Rpn10 subunit of 26S proteasomes with the ubiquitin-like domain

Parkin 将 26S 蛋白酶体的 Rpn10 亚基与泛素样结构域结合

• 发表时间: 2003
• 期刊: EMBO Rep. 4
• 作者: Sakata;E.;Yamaguchi;Y.;Kurimoto;E.;Kikuchi;J.;Yokoyama;S.;Yamada;S.;Kawahara;H.;Yokosawa;H.;Hattori;N.;Mizuno;Y.;Tanaka;K.;Kato;K.
• 通讯作者: K.

Sakata, E., Yamaguchi, Y., Kurimoto, E., Kikuchi, J., Yokoyama, S., Yamada, S., Kawahara, H., Yokosawa, H., Hattori, N., Mizuno, Y., Tanaka, K., Kato, K.: "Parkin binds the Rpn10 subunit of 26S proteasomes with the ubiquitin-like domain"EMBO Rep.. (in pre

坂田 E.、山口 Y.、栗本 E.、菊池 J.、横山 S.、山田 S.、川原 H.、横泽 H.、服部 N.、水野 Y.、