Tanaka Nobuyuki, Kyuuma Masanao, Sugamura Kazuo
Department of Microbiology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Cancer Sci. 2008 Jul;99(7):1293-303. doi: 10.1111/j.1349-7006.2008.00825.x. Epub 2008 Apr 22.
Endosomal sorting complex required for transport (ESCRT) proteins form a multicomplex sorting machinery that controls multivesicular body (MVB) formation and the sorting of ubiquitinated membrane proteins to the endosomes. Being sorted to the MVB generally results in the lysosome-dependent degradation of cell-surface receptors, and defects in this machinery induce dysregulated receptor traffic and turnover. Recent lessons from gene targeting and silencing methodologies have implicated the ESCRT in normal development, cell differentiation, and growth, as well as in the budding of certain enveloped viruses. Furthermore, it is becoming apparent that the dysregulation of ESCRT proteins is involved in the development of various human diseases, including many types of cancers and neurodegenerative disorders. Here, we summarize the roles of ESCRT proteins in MVB sorting processes and the regulation of tumor cells, and we discuss some of their other functions that are unrelated to vesicular transport.
转运所需的内体分选复合体(ESCRT)蛋白形成一种多复合体分选机制,该机制控制多泡体(MVB)的形成以及泛素化膜蛋白向内体的分选。被分选到MVB通常会导致细胞表面受体通过溶酶体依赖性降解,并且该机制中的缺陷会诱导受体运输和周转失调。基因靶向和沉默方法的最新研究结果表明,ESCRT参与正常发育、细胞分化和生长,以及某些包膜病毒的出芽。此外,越来越明显的是,ESCRT蛋白的失调与多种人类疾病的发生发展有关,包括多种类型的癌症和神经退行性疾病。在这里,我们总结了ESCRT蛋白在MVB分选过程中的作用以及对肿瘤细胞的调控,并讨论了它们与囊泡运输无关的其他一些功能。