The unique functions of tissue-specific proteasomes

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.