Inhibitions of the proteasome and aggresome pathways by bortezomib and DACi. Unfolded and/or misfolded proteins are targeted by ubiquitin for degradation by the proteasome and aggresome pathways. Inhibitions of the proteasome and aggresome pathways by bortezomib and DACi. Unfolded and/or misfolded proteins are targeted by ubiquitin for degradation by the proteasome and aggresome pathways. The proteasome inhibitor bortezomib leads to the accumulation of ubiquitin protein aggregates. These aggregates are shuttled to the lysosome, where they are degraded via the aggresome pathway. Aggresome formation involves the shuttling of the protein aggregates along microtubules by dynein motor proteins. The interaction of the unfolded and/or misfolded protein complexes is facilitated by HDAC6. Conversely, DACi with inhibitory activity toward HDAC6 blocks this process. The combination of proteasome inhibitors and DACi leads to increased cellular stress and apoptosis. Teru Hideshima et al. Mol Cancer Ther 2011;10:2034-2042 ©2011 by American Association for Cancer Research