Figure 5.

Inhibitions of the proteasome and aggresome pathways. Misfolded proteins are ubiquitinated for degradation by the proteasome and aggresome pathways. The proteasome inhibitors lead to the accumulation of ubiquitin-protein aggregates. These aggregates are transported to the lysosome, where they are degraded by the aggresome pathway. The interaction of the unfolded and/or misfolded protein complexes is facilitated by histone deacetylase 6 (HDAC6) and HDACi blocks this process. The combination of proteasome inhibitors (PI) and histone deacetylase inhibitor (HDACi) leads to increased cellular stress and apoptosis. Adapted from Hideshima et al. [153].