Molecular basis of hsp90 inhibitor-induced sensitization of MM cells to proteasome inhibitor bortezomib. In vitro treatment of chemo- and bortezomib-resistant primary MM tumor cells with bortezomib (PS-341, 5 nM, 12 hours), 17-AAG (250 nM, 12 hours) or their combination indicates that the combination of the 2 drugs induces more pronounced (A) accumulation of ubiquitinated proteins, as shown by immunoblotting analysis, and (B) inhibition of proteasome activity, evidenced by 20S proteasome chymotryptic activity assay, than either drug alone. Error bars indicate SD.