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

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  • Takanashi Yusuke
    Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine First Department of Surgery, Hamamatsu University School of Medicine
  • Kahyo Tomoaki
    Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine
  • Kamamoto Sae
    Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine
  • Zhang Hengsen
    Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine
  • Chen Bin
    Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine
  • Ping Yashuang
    Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine
  • Mizuno Kiyomichi
    First Department of Surgery, Hamamatsu University School of Medicine
  • Kawase Akikazu
    First Department of Surgery, Hamamatsu University School of Medicine
  • Koizumi Kei
    First Department of Surgery, Hamamatsu University School of Medicine
  • Satou Masanori
    First Department of Surgery, Hamamatsu University School of Medicine
  • Funai Kazuhito
    First Department of Surgery, Hamamatsu University School of Medicine
  • Shiiya Norihiko
    First Department of Surgery, Hamamatsu University School of Medicine
  • Setou Mitsutoshi
    Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine International Mass Imaging Center, Hamamatsu University School of Medicine Department of Systems Molecular Anatomy, Institute for Medical Photonics Research, Hamamatsu University School of Medicine

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<p>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.</p><p>Key words: UBL3, small extracellular vesicles, protein sorting, ubiquitin-like protein, post-translational modification</p>

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