Molecular mechanism in regulation of the intramembrane proteases

膜内蛋白酶调节的分子机制

• 批准号: 23657082
• 负责人: FUTAI Eugene
• 金额: $ 2.58万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-23657082/
• 关键词: 酵素; プロテアーゼ; 脳・神経; 認知症; 酵母

Since intramenbrane proteases possess these active sites buried in the lipid bilayer, it is difficult to purify and measure their activities. We introduced human gamma-secretase complex in yeast and succeeded in measuring its activity in vitro with the yeast microsomes. In this research, we utilized the reconstition system and analyzed the enzymatic character of the gamma-secretase. We found the relationship between proteolytic activities and subunit composition, and we screened the modulator of the protease activities from lipids and natural compounds. Malfunction of gamma-secretase leads to Alzheimer's disease. We would like to expand our research to the treatment of the disease.

由于膜内蛋白酶具有这些活性位点埋在脂质双层，这是很难纯化和测量它们的活动。我们将人γ-分泌酶复合物引入酵母中，并成功地用酵母微粒体在体外测定了其活性。本研究利用重组体系对γ-分泌酶的酶学性质进行了分析。我们发现了蛋白水解活性与亚基组成之间的关系，并从脂质和天然化合物中筛选出蛋白酶活性的调节剂。γ-分泌酶功能障碍导致阿尔茨海默病。我们想把研究扩展到治疗这种疾病上。

项目成果

プロリン異性化酵素Pin1 はPresenilin に結合し, 活性を制御する

脯氨酸异构酶 Pin1 与早老素结合并调节其活性

• 发表时间: 2013
• 作者: 佐々木広美;二井勇人;内田隆史
• 通讯作者: 内田隆史

Tumor suppressor cell adhesion molecule 1 (CADM1) is cleaved by a disintegrin and metalloprotease 10 (ADAM10) and subsequently cleaved by γ-secretase complex

• DOI: 10.1016/j.bbrc.2011.11.140
• 发表时间: 2012-01-06
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Nagara, Yusuke;Hagiyama, Man;Ishiura, Shoichi
• 通讯作者: Ishiura, Shoichi

酵母再構成系を用いたγセクレターゼの機能解析

使用酵母重组系统对γ-分泌酶进行功能分析

• 发表时间: 2013
• 作者: 米村洋而;二井勇人;柳下聡介;周防諭;石浦章一
• 通讯作者: 石浦章一

Comparison of Presenilin 1 and Presenilin 2 γ-Secretase Activities Using a Yeast Reconstitution System*

• DOI: 10.1074/jbc.m111.270108
• 发表时间: 2011-11
• 期刊: The Journal of Biological Chemistry
• 作者: Y. Yonemura;E. Futai;Sosuke Yagishita;S. Suo;T. Tomita;T. Iwatsubo;S. Ishiura

プロリン異性化酵素Pin1はPresenilin1に結合し、活性を制御する

脯氨酸异构酶 Pin1 与 Presenilin1 结合并调节其活性

• 发表时间: 2013
• 作者: 佐々木広美;二井勇人;内田隆史
• 通讯作者: 内田隆史