LC3 conjugation system in mammalian autophagy.
LC3 conjugation system in mammalian autophagy.
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DOI：
10.1016/j.biocel.2004.05.009
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发表时间：
2004-12
期刊：
影响因子：
--
通讯作者：
Kominami E
中科院分区：
文献类型：
--
作者：
Tanida I;Ueno T;Kominami E
自噬是蛋白质和细胞器的大量降解，是哺乳动物细胞维持、细胞活力、分化和发育所必需的过程。自噬与神经退行性疾病、心肌病、癌症、程序性细胞死亡以及细菌和病毒感染有显著关联。在自噬过程中，杯状结构，即前自噬体，吞噬细胞溶质组分，包括细胞器，并关闭，形成自噬体，其随后与溶酶体融合，导致溶酶体溶解酶对自噬体的内部组分进行蛋白水解降解。在哺乳动物自噬体的形成过程中，需要两种泛素化样修饰，Atg 12-缀合和LC 3-修饰。LC 3是酵母Atg 8的自噬体直系同源物。LC 3的脂化形式LC 3-II已被证明是哺乳动物中的自噬体标记物，并已被用于研究神经退行性疾病和神经肌肉疾病、肿瘤发生以及细菌和病毒感染中的自噬。其他Atg 8同源物GABARAP和GATE-16也通过相同的机制进行修饰。在非饥饿大鼠中，LC 3-II的组织分布不同于GABARAP和GATE-16、GABARAP-II和GATE-16-II的脂化形式，表明这三种修饰蛋白之间存在功能差异。LC 3-II和GABARAP-II的去脂由hAtg 4 B介导。本文综述了LC 3修饰的分子机制、LC 3修饰与哺乳动物Atg 12缀合之间的串扰、hAtg 4 B介导的LC 3脂化和去脂化循环以及最近关于另外两个Atg 8同系物GABARAP和GATE-16的研究结果。我们还强调了最近关于LC 3修饰的病理生物学的发现，包括其在微生物感染，癌症和神经肌肉疾病中的作用。
Autophagy is the bulk degradation of proteins and organelles, a process essential for cellular maintenance, cell viability, differentiation and development in mammals. Autophagy has significant associations with neurodegenerative diseases, cardiomyopathies, cancer, programmed cell death, and bacterial and viral infections. During autophagy, a cup-shaped structure, the preautophagosome, engulfs cytosolic components, including organelles, and closes, forming an autophagosome, which subsequently fuses with a lysosome, leading to the proteolytic degradation of internal components of the autophagosome by lysosomal lytic enzymes. During the formation of mammalian autophagosomes, two ubiquitylation-like modifications are required, Atg12-conjugation and LC3-modification. LC3 is an autophagosomal ortholog of yeast Atg8. A lipidated form of LC3, LC3-II, has been shown to be an autophagosomal marker in mammals, and has been used to study autophagy in neurodegenerative and neuromuscular diseases, tumorigenesis, and bacterial and viral infections. The other Atg8 homologues, GABARAP and GATE-16, are also modified by the same mechanism. In non-starved rats, the tissue distribution of LC3-II differs from those of the lipidated forms of GABARAP and GATE-16, GABARAP-II and GATE-16-II, suggesting that there is a functional divergence among these three modified proteins. Delipidation of LC3-II and GABARAP-II is mediated by hAtg4B. We review the molecular mechanism of LC3-modification, the crosstalk between LC3-modification and mammalian Atg12-conjugation, and the cycle of LC3-lipidation and delipidation mediated by hAtg4B, as well as recent findings concerning the other two Atg8 homologues, GABARAP and GATE-16. We also highlight recent findings regarding the pathobiology of LC3-modification, including its role in microbial infection, cancer and neuromuscular diseases.
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酵母突变体在细胞质中的分离和表征与液泡蛋白靶向途径的分离。
影响因子：
7.8
作者：
HARDING, TM;MORANO, KA;SCOTT, SV;KLIONSKY, DJ
通讯作者：
KLIONSKY, DJ
影响因子：
64.8
作者：
Ichimura, Y;Kirisako, T;Ohsumi, Y
通讯作者：
Ohsumi, Y
DOI：
10.1083/jcb.152.3.519
发表时间：
2001-02-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kihara A;Noda T;Ishihara N;Ohsumi Y
通讯作者：
Ohsumi Y
影响因子：
3.5
作者：
Kametaka, S;Matsuura, A;Ohsumi, Y
通讯作者：
Ohsumi, Y
影响因子：
8
作者：
Aki, T;Yamaguchi, K;Mizukami, Y
通讯作者：
Mizukami, Y