Roles of APGubiquitylation-like modification during differentiation and maintenance of neuronal cells.

APG泛素化样修饰在神经元细胞分化和维持过程中的作用。

• 批准号: 15590254
• 负责人: ISEI Tanida
• 金额: $ 2.24万
• 依托单位: JUNTENDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590254/
• 关键词: AUTOPHAGY; UBIQUITYLATION-LIKE; ATG; APG gene; MAP-LC3; GABARAP; GATE-16; 3rd Cell Death; DIFFERENTIATION TO NEURON; タンパク質分解; APG10; ATG10; APG7; ATG7; APG遣伝子

ATG-ubiquitylation-like modification is essential for autophagy in yeast, plant, and mammals. ATG7 is a key enzyme essential for the reaction. We generated a conditional knock-out mouse of ATG7 Mouse liver lacking Atg7 resulted in a severe hepatomegaly with inflammation, leading to a loss of viability under starvation. During generating the conditional mouse, we showed that human Atg4B is an unique cysteine protease for carboxyl cleavage of LC, GABARAP, and GATE-16, and is delipidating enzyme for LC3-and GABARAP-phospholipid conjugate. Furthermore, we showed that human LC3 is an authentic modifier mediated by human Atg7 and Atg3. We also found a novel Ufml Ubl-modification system in mammals. In addition, we investigated several aspects of ATG-conjugation systems; Strauctural analysis of LC3 by NMR, Role of Rab7 in autophagy, and tissue-distribution of modified forms of LC3, GABARAP, and GATE-16. Now, we are generating a brain-specific ATG7-knockout mouse that will be a definitive tool for analyses of relations between autophagy and neurodegenerative diseases

ATG - 泛素化的修饰对于酵母，植物和哺乳动物的自噬至关重要。 ATG7是反应必不可少的关键酶。我们产生了缺乏ATG7的ATG7小鼠肝脏的有条件的敲除小鼠，导致严重的肝肿大，炎症，导致饥饿下的生存力丧失。在生成条件小鼠的过程中，我们表明人ATG4B是一种独特的半胱氨酸蛋白酶，用于LC，Gabarap和Gate-16的羧基裂解，并且正在为LC3和Gabarap-磷脂结合物删除酶。此外，我们表明人LC3是由人ATG7和ATG3介导的真实修饰符。我们还发现了一种新型的UFML UBL修饰系统。此外，我们研究了ATG结合系统的几个方面。 NMR对LC3的横向分析，Rab7在自噬中的作用以及LC3，Gabarap和Gate-16的修饰形式的组织分布。现在，我们正在生成一种大脑特异性的ATG7敲除鼠标，这将是分析自噬和神经退行性疾病之间关系的确定工具

项目成果

谷田 以誠, 木南 英紀: "オートファジーにおけるApg7タンパク質活性化酵素"生体の科学. 54. 521-527 (2003)

Isei Tanida、Hideki Kinami：“自噬中的 Apg7 蛋白激活酶”《生物科学》54. 521-527 (2003)。

Ueno.T,.Tanida.I., Kominami, E.: ""Autophagy and Nueromuscular Disease" in Autophagy, Klionsky, D.J.Eds."Eurekah.com Landes Bioscience. 264-286 out of 311 (2004)

Ueno.T,.Tanida.I., Kominami, E.：“自噬中的“自噬和神经肌肉疾病”，Klionsky，D.J.Eds。”Eurekah.com Landes Bioscience。

Role for Rab7 in maturation of late autophagic vacuoles

• DOI: 10.1242/jcs.01370
• 发表时间: 2004-09-15
• 期刊: JOURNAL OF CELL SCIENCE
• 影响因子: 4
• 作者: Jäger, S;Bucci, C;Eskelinen, EL
• 通讯作者: Eskelinen, EL

Autophagy (Chapter 22: Autophagy and Neuromuscular Diseases)

自噬（第 22 章：自噬和神经肌肉疾病）

• 发表时间: 2004
• 作者: Ueno et al.(Klionsky Eds)

Nemoto T, Tanida I, Tanida-Miyake E, Minematsu-Ikeguchi N, Yokota M, Ohsumi M, Ueno T, Kominami E.: "The mouse APG10 homologue, an E2-like enzyme for Apg12p conjugation, facilitates MAP-LC3 modification."Journal of Biological Chemistry. 278. 39517-39526 (

Nemoto T、Tanida I、Tanida-Miyake E、Minematsu-Ikeguchi N、Yokota M、Ohsumi M、Ueno T、Kominami E.：“小鼠 APG10 同源物是一种用于 Apg12p 缀合的 E2 样酶，可促进 MAP-LC3 修饰。