Molecular basis of protein cross-linking reactions for cellular functions

细胞功能蛋白质交联反应的分子基础

• 批准号: 23380200
• 负责人: HITOMI Kiyotaka
• 金额: $ 12.73万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23380200/
• 关键词: 酵素; 蛋白質架橋; 細胞機能

Transglutaminases are the enzymes that catalyze protein cross-linking or modification via peptide-bound glutamine residues. These reactions are essential for the multiple biological processes such as blood coagulation, skin epidermis formation and apoptosis. In order to elucidate the physiological roles and expression sites on mammals, using highly reactive substrate peptides (obtained by us for these years), we analyzed expression pattern and established identification system of possible substrates. In the studies, expressions for RNA, protein (using antibody), in situ enzymatic activity were investigated. Furthermore, establishment of FRET system to detect intracellular activity was attempted. As a result, in vitro system was successful. In addition, Medaka (Oryzias latepis) as a model animal, was analyzed for the orthologues of transglutaminases: biochemical data and establishment of a couple of genetic loss fish was produced.

转氨酶是通过肽结合的谷氨酰胺残基催化蛋白质交联或修饰的酶。这些反应对于血液凝固、皮肤表皮形成和细胞凋亡等多种生物学过程是必不可少的。为了阐明其在哺乳动物中的生理作用和表达位点，我们利用近年来获得的高活性底物肽，分析了其表达模式，并建立了可能底物的鉴定系统。在研究中，RNA，蛋白质（使用抗体）的表达，原位酶活性进行了研究。此外，尝试建立FRET系统来检测细胞内活性。结果表明，体外培养系统是成功的。此外，以青鳉为模式动物，分析了青鳉转氨酶的直向同源物：获得了生化数据，并建立了一对遗传缺失鱼。

项目成果

Hornerin is a component of the epidermal comified cell envelopes

Hornerin 是表皮复合细胞被膜的成分

• 发表时间: 2011
• 期刊: FASEB J.
• 作者: Henry J;Hitomi K.;Simon M.;(他8名)
• 通讯作者: (他8名)

Characterization of medaka transglutaminases, a protein cross-linking enzyme family

青鳉转谷氨酰胺酶（蛋白质交联酶家族）的表征

• 发表时间: 2011
• 作者: 斉藤麻衣;伊藤みほ;人見清隆
• 通讯作者: 人見清隆

Knocking-in the R142C mutation in transglutaminase 1 disrupts the stratum corneum barrier and postnatal survival of mice.

敲入转谷氨酰胺酶 1 中的 R142C 突变会破坏小鼠的角质层屏障和出生后存活。

• 发表时间: 2012
• 期刊: J Dermatol Sci
• 影响因子: 4.6
• 作者: Nakagawa N;Yamamoto M;Imai Y;Sakaguchi Y;Takizawa T;Ohta N;Yagi N;Hatta I;Hitomi K;Takizawa T;Takeda J;Tsuda T;Matsuki M;Yamanishi K
• 通讯作者: Yamanishi K

皮膚表皮におけるタンパク質架橋化酵素の基質ペプチド探索と関連疾患診断への活用

寻找皮肤表皮蛋白交联酶的底物肽及其用于相关疾病的诊断

• 发表时间: 2013
• 作者: 人見清隆;山崎梨沙;鞍本克真;辰川英樹
• 通讯作者: 辰川英樹

Identification and application of highly reactive peptide substrate for mammalian transglutaminas, a protein cross-linking enzyme

哺乳动物转谷氨酰胺（一种蛋白质交联酶）高活性肽底物的鉴定和应用

• 发表时间: 2012
• 作者: 菅沼名津季;斉藤麻衣;辰川英樹;人見清隆;Kiyotaka HITOMI;人見清隆;人見清隆;人見清隆
• 通讯作者: 人見清隆