Proteasome inhibitors and antigen presentation

Protein degradation plays an important role in the control and regulation of many crucial biological functions, ranging from cell cycle progression to presentation of viral antigens for scrutiny by cells of the immune system. At the heart of many of these catabolic events is the multicatalytic proteinase complex known as the proteasome. This large barrel-shaped protein complex executes a remarkable set of functions ranging from the complete destruction of abnormal and misfolded proteins to the specific proteolytic activation of crucial signaling molecules. Inhibitors of this proteolytic complex have thus been extremely useful for perturbing its function and deciphering its role in these diverse biological processes. Inhibitors of the proteasome consist mainly of peptides that are modified at the predicted site of hydrolysis with a reactive functional group capable of modifying the attacking nucleophile, either reversibly or irreversibly. Many of these inhibitors can be used in living cells and have proved to be invaluable tools for the study of proteasome function.