Ubiquitin-like 3 as a new protein-sorting factor for small extracellular vesicles

Cell Struct Funct. 2022;47(1):1-18. doi: 10.1247/csf.21078.

Abstract

Ubiquitin-like 3 (UBL3) is a well-conserved ubiquitin-like protein (UBL) in eukaryotes and regulates the ubiquitin cascade, but the significant roles of UBL3 in cellular processes remained unknown. Recently, UBL3 was elucidated to be a post-translational modification factor that promotes protein sorting to small extracellular vesicles (sEVs). Proteins sorted into sEVs have been studied as etiologies of sEV-related diseases. Also, there have been attempts to construct drug delivery systems (DDSs) by loading proteins into sEVs. In this review, we introduce the new concept that UBL3 has a critical role in the protein-sorting system and compare structure conservation between UBL3 and other UBLs from an evolutionary perspective. We conclude with future perspectives for the utility of UBL3 in sEV-related diseases and DDS.Key words: UBL3, small extracellular vesicles, protein sorting, ubiquitin-like protein, post-translational modification.

Keywords: UBL3; post-translational modification; protein sorting; small extracellular vesicles; ubiquitin-like protein.

Publication types

  • Review

MeSH terms

  • Animals
  • Extracellular Vesicles* / metabolism
  • Humans
  • Protein Processing, Post-Translational
  • Protein Transport
  • Ubiquitin / metabolism
  • Ubiquitins / genetics
  • Ubiquitins / metabolism*

Substances

  • UBL3 protein, human
  • Ubiquitin
  • Ubiquitins

Grants and funding

This work was supported by grants from Japan Agency for Medical Research and Development (AMED) [Grant Number JP20gm0910004] and MEXT Project for promoting public utilization of advanced research infrastructure (Program for supporting the construction of core facilities, Grant Number JPMXS0450200221).