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タンパク質品質管理を担うシャペロン依存型ユビキチンリガーゼCHIPの遺伝学的解析

CHIP 的遗传分析，一种负责蛋白质质量控制的分子伴侣依赖性泛素连接酶

基本信息

批准号：
15032263
负责人：
小松雅明
金额：
$ 5.38万
依托单位：
Juntendo University (2004)Tokyo Metropolitan Organization for Medical Research (2003)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

CHIP欠損マウスの作製に成功し、表現型の解析を行った。CHIP欠損マウスは失調様歩行を示すことから、神経細胞において重要な働きをしていることが示唆され、現在詳細を解明中である。またCHIPの新しいパートナーシャペロンとしてHsj-1を発見した。Hsj-1はポリユビキチン鎖結合ドメインを有するDnaJファミリー分子であり、CHIPによる異常タンパク質のユビキチン化を促進することを明らかにした。二つのユビキチン様修飾システム(Atg,Ufm1システム)に焦点をおき、それらの機能、個体レベルにおける生理的意義について解析を進めている。Atgシステムに関しては、Atgシステムの活性化酵素であるAtg7を肝臓特異的に欠損したマウスを作製、解析した。その結果、オートファジー不能マウスは栄養飢餓に対する蛋白質分解阻害のみならず定常状態においてもユビキチン陽性封入体や異常オルガネラの蓄積を引き起こすことを見いだした(Komatsu et al.投稿中)。この研究は、オートファジーによる異常蛋白質・オルガネラの除去機構の存在を強く示唆する。また、Atg蛋白質と相互作用する新奇E1様酵素(Uba5)を同定し、Uba5によって活性化されるモディファイヤー分子(Ufm1)及びUfm1のE2酵素(Ufc1)を同定した。また、Ufm1は細胞内において複数の蛋白質と共有結合することを明らかにした。すなわち新奇ユビキチン様修飾システムを発見した(Komatsu et al.EMBO J.2004)。Ufm1システムは後生動物、植物に保存されているが酵母には存在せず、多細胞生物おいて重要な役割を担うと考えられる。この研究は、蛋白質修飾システムに新たな研究展開を提供した。

CHIP is not responsible for success and table resolution for row resolution. CHIP is in the process of instigating information. It is now in the process of understanding that it is important to show that the information is not correct. The CHIP is new. I am sorry. I have a new CHIP. The combination of the Hsj-1 information system and the CHIP information system has been used to improve the performance of the system. In this way, the molecular structure of the DnaJ system, the molecular weight of the molecule and the molecular weight of the molecule have been detected. In this paper, the meaning of the physiology of the focus, the mechanism and the physiology of the Atg,Ufm1 patients are analyzed. Atg enzyme, Atg7 enzyme, Atg7 enzyme, enzyme. The results showed that there was no significant difference in the results of this study. The results showed that there was no significant difference in the results of this study. The results showed that there was no significant difference in the results of this study. The results showed that there was no significant difference in the results of this study. The results showed that there was no significant difference between the two groups. The results showed that there was no significant difference between the two groups. The results showed that there was no significant difference between the two groups. The results showed that there was no significant difference between the two groups. The results showed that there was no significant difference in the results. The results showed that there was no significant difference between the two groups. The results showed that there was no significant difference between the two groups. The results showed that there was no significant difference between the two groups. The results showed that there was no significant difference between the two groups. The results showed that there was no significant difference in the In the contribution). There is a strong indication that there is a strong mechanism for the removal of human troponin. Atg protein interaction, novel E1 enzyme (Uba5), Uba5 enzyme activation (Ufm1) and Ufm1 E2 enzyme (Ufc1). There is a total number of proteins in the cells of both Ufm1 and Cellular.There is a common combination of proteins. I don't know what's new. I don't know. (Komatsu et al.EMBO J.2004). Ufm1 animals and plants are preserved, yeast is present, and multicellular organisms are important to be cut. The development of research and protein research will provide information on new research.