Fig. 4

Aggresome pathway and synergy with proteasome inhibitors. Ubiquitin targets unfolded and/or misfolded proteins for destruction via the proteasome and aggresome pathways. Inhibiting proteasome pathways with inhibitors like bortezomib or carfilzomib results in the formation of ubiquitin protein aggregates, which are subsequently shuttled to the lysosome and destroyed via the aggresome pathway. Protein aggregates migrate across microtubules utilizing the dynein motor protein in the aggregation process. HDAC-6 promotes protein aggregate/microtubule complexes. If histone deacetylase (HDAC) is inhibited (together with proteasome inhibitors) at this moment, ubiquitin protein aggregates would develop further, resulting to apoptosis. If histone deacetylase (HDAC) is inhibited (together with proteasome inhibitors) at this moment, ubiquitin protein aggregates would develop further, resulting to apoptosis. Figure created with BioRender.com