Altering protein turnover in tumor cells: New opportunities for anti-cancer therapies

The promising effects of the proteasome inhibitor bortezomib (Velcade, PS-341) in the treatment of certain types of cancer have fired up the interest on this multicatalytic proteolytic machinery. A number of recent reviews thoroughly describe various aspects of the ubiquitin-proteasome system and its importance in the control of cell growth and tumorigenesis. Here, we will focus on recent data unveiling a link between the proteasome and some elements of the apoptotic machinery including Bcl-2 members, caspases, IAPs and IAP antagonists. Perturbing their turnover significantly contributes to the apoptotic response and the anti-neoplastic activity of proteasome inhibitors.