ABSTRACT

K nowledge about physio logical functions of the proteasome, its biochemical mechanisms, and its importance in cell regulation have developed rather slowly, in large part because of difficulties in measuring rates of protein turnover in vivo and in dissecting the roles of the cell’s different degradative systems. The past few years have witnessed dramatic progress in these areas, in part through the identi­ fication of pharmacological inhibitors of the proteasome that can readily enter cells and selectively inhib it proteasome-mediated protein degradation. These inhibitors have greatly simplified in vivo studies of the function of the ubiquitin-proteasome pathway, and have led to many insights about the physiological importance of this process. This artic le reviews the properties of these proteasome inhibitors and a number of unex­ pected findings that have emerged from their use.