The unique functions of tissue-specific proteasomes

Trends Biochem Sci. 2014 Jan;39(1):17-24. doi: 10.1016/j.tibs.2013.10.004. Epub 2013 Nov 26.


The 26S proteasome is the main protease in eukaryotes. Proteolysis occurs within the cylindrical 20S proteasome that is constitutively expressed in most tissues. However, three tissue-specific versions of the 20S proteasome have been discovered to date. The immunoproteasome is optimized to process antigens and it directs the differentiation of T helper (Th) cells. The thymoproteasome is selectively expressed in cortical epithelial cells of the thymus where it plays an essential role in the positive selection of T lymphocytes. Finally, the spermatoproteasome is found in the testes where it is required during spermatogenesis. Here, we outline how tissue-specific proteasomes adapt to functional needs in their respective tissues and how their selective inhibition may be used to interfere with autoimmune diseases and cancer.

Keywords: antigen presentation; immunoproteasome; spermatoproteasome; thymoproteasome; ubiquitin.

Publication types

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

MeSH terms

  • Animals
  • Antigen Presentation
  • Archaeal Proteins / chemistry
  • Archaeal Proteins / physiology
  • Autoimmune Diseases / enzymology
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / physiology
  • Cell Differentiation
  • Humans
  • Organ Specificity
  • Proteasome Endopeptidase Complex / chemistry
  • Proteasome Endopeptidase Complex / physiology*
  • Protein Structure, Quaternary
  • Proteolysis
  • Ubiquitinated Proteins / metabolism


  • Archaeal Proteins
  • Bacterial Proteins
  • Ubiquitinated Proteins
  • Proteasome Endopeptidase Complex