| dc.description.abstract | Proteasomes are large protein complexes capable of degrading poly-ubiquitylated proteins. They function in the degradation of misfolded and damaged proteins and in many other cellular processes. Upon induction of the immunomodulatory cytokine interferon γ, the proteasomal catalytic subunits are substituted for the catalytic immunosubunits. These proteasomes are called immunoproteasomes and possess altered cleavage site specificity. For a long time they have only been implicated in antigen presentation. Immunoproteasomes were shown to be more efficient in the generation of antigenic peptides presented by MHC class I molecules. However, processing of several antigenic peptides required the presence of the standard proteasome and they were destroyed by immunoproteasomes, indicating that immunoproteasomes do not solely function in antigen presentation. Immunoproteasomes have indeed been implicated in other immune-related processes, including cytokine production. Interestingly, immunoproteasome expression has also been observed in non-immune cells and immune-privileged tissues, suggesting a function beyond immunity. Indeed, these proteasomes were found to be more efficient in the clearance of poly-ubiquitylated proteins and aggresomes upon stress and thereby in the maintenance of protein homeostasis and cell viability. Which of the immune or non-immune functions is executed by the immunoproteasomes might be dependent on the cell type expressing these proteasomes. Understanding the mechanisms of immunoproteasome functioning will be an important field of research and may help in the development of new treatments for many diseases. | |
