Figure 2.

Inhibitions of the proteasome and aggresome pathways by bortezomib and deacetylase inhibitors (DACi). Unfolded/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/misfolded protein complexes is facilitated by histone deacetylase 6 (HDAC6). Conversely, DACi with inhibitory activity toward HDAC6 block this process. The combination of proteasome inhibitors and DACi lead to increased cellular stress and apoptosis.