PROTEASOME INHIBITORS AND ANTIGEN PRESENTATION

Protein degradation plays an important role in the control and regulat ion of many crucial biological functions, ranging from cell cycle prog ression 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 r anging from the complete destruction of abnormal and misfolded protein s to the specific proteolytic activation of crucial signaling molecule s. Inhibitors of this proteolytic complex have thus been extremely use ful for perturbing its function and deciphering its role in these dive rse 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 nucleo phile, either reversibly or irreversibly. Many of these inhibitors can be rued in living cells and have proven to be invaluable tools for th e study of proteasome function. (C) 1997 John Wiley & Sons, Inc.