Beyond cells: The extracellular circulating 20S proteasomes

Biochim Biophys Acta Mol Basis Dis. 2021 Mar 1;1867(3):166041. doi: 10.1016/j.bbadis.2020.166041. Epub 2020 Dec 16.

Abstract

Accumulating evidence arising from numerous clinical studies indicate that assembled and functional 20S proteasome complexes circulate freely in plasma. Elevated levels of this core proteolytic complex have been found in the plasma of patients suffering from blood, skin and solid cancers, autoimmune disorders, trauma and sepsis. Moreover, in various diseases, there is a positive correlation between circulating 20S proteasome (c20S) levels and treatment efficacy and survival rates, suggesting the involvement of this under-studied c20S complex in pathophysiology. However, many aspects of this system remain enigmatic, as we still do not know the origin, biological role or mechanisms of extracellular transport and regulation of c20S proteasomes. In this review, we provide an overview of the current understanding of the c20S proteasome system and discuss the remaining gaps in knowledge.

Keywords: 20S proteasome; Blood plasma; Pathophysiology; Protein degradation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / blood
  • Autoimmune Diseases / metabolism
  • Burns / blood
  • Burns / metabolism
  • Hematologic Neoplasms / blood
  • Hematologic Neoplasms / metabolism
  • Humans
  • Neoplasms / blood
  • Neoplasms / metabolism
  • Proteasome Endopeptidase Complex / blood*
  • Proteasome Endopeptidase Complex / metabolism
  • Proteolysis
  • Sepsis / blood
  • Sepsis / metabolism

Substances

  • Proteasome Endopeptidase Complex