UAE inhibition does not impact upon proteasome function. (A) Accumulation of ubiquitin (Ub)-protein conjugates was evaluated in the indicated cell lines after exposure to TAK-243, bortezomib, or to the combination of the 2 agents at the indicated concentrations for 24 hours. (B) RPMI 8226 and ANBL-6 cells transfected with a vector expressing the ZsGreen-MODC-d410 fusion protein were exposed to TAK-243 or bortezomib at the indicated concentrations. Expression levels of this protein, which is degraded in a proteasome-dependent but ubiquitin-independent manner, were then evaluated by fluorescence monitoring, and the panel shows fluorescence (λ_ex 488 nM/λ_em 510 nM). (C) MM1.S and U266 cells were then exposed to TAK-243 or bortezomib under the conditions described in panel A, and western blotting was used to determine the abundance of MCL1 and cMYC.