Division for Therapies Against Intractable Diseases, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
Cell Mol Life Sci. 2019 Dec;76(24):4829-4848. doi: 10.1007/s00018-019-03246-7. Epub 2019 Jul 30.
Exosomes, a type of small extracellular vesicles (sEVs), are secreted membrane vesicles that are derived from various cell types, including cancer cells, mesenchymal stem cells, and immune cells via multivesicular bodies (MVBs). These sEVs contain RNAs (mRNA, miRNA, lncRNA, and rRNA), lipids, DNA, proteins, and metabolites, all of which mediate cell-to-cell communication. This communication is known to be implicated in a diverse set of diseases such as cancers and their metastases and degenerative diseases. The molecular mechanisms, by which proteins are modified and sorted to sEVs, are not fully understood. Various cellular processes, including degradation, transcription, DNA repair, cell cycle, signal transduction, and autophagy, are known to be associated with ubiquitin and ubiquitin-like proteins (UBLs). Recent studies have revealed that ubiquitin and UBLs also regulate MVBs and protein sorting to sEVs. Ubiquitin-like 3 (UBL3)/membrane-anchored Ub-fold protein (MUB) acts as a post-translational modification (PTM) factor to regulate efficient protein sorting to sEVs. In this review, we focus on the mechanism of PTM by ubiquitin and UBLs and the pathway of protein sorting into sEVs and discuss the potential biological significance of these processes.
外泌体是一种小的细胞外囊泡 (sEVs)，通过多泡体 (MVBs) 从各种细胞类型（包括癌细胞、间充质干细胞和免疫细胞）中分泌出来。这些 sEVs 包含 RNA（mRNA、miRNA、lncRNA 和 rRNA）、脂质、DNA、蛋白质和代谢物，所有这些都介导细胞间通讯。这种通讯被认为与多种疾病有关，如癌症及其转移和退行性疾病。蛋白质被修饰并分类到 sEVs 的分子机制尚不完全清楚。各种细胞过程，包括降解、转录、DNA 修复、细胞周期、信号转导和自噬，已知与泛素和泛素样蛋白 (UBLs) 有关。最近的研究表明，泛素和 UBLs 也调节 MVBs 和蛋白质向 sEVs 的分类。泛素样蛋白 3 (UBL3)/膜锚定 Ub 折叠蛋白 (MUB) 作为一种翻译后修饰 (PTM) 因子，调节蛋白质向 sEVs 的有效分类。在这篇综述中，我们重点介绍泛素和 UBLs 的 PTM 机制以及蛋白质向 sEVs 分类的途径，并讨论这些过程的潜在生物学意义。
