Figure 4

The summary of possible bortezomin resistance mechanisms. The mechanisms of proteasome inhibitor bortezomib resistance mainly focused on the modifications of the mechanisms of its action. Mutations at key points of β5 subunit of proteasome (PSMB5) decrease the affinity of the PSMB5 to bortezomb, which result in the decreased inhibition of the chymotrypsin-like activity, up-regulation of proteasome subunits contributing to the high basal levels of proteasome activity, alterations of gene and protein expression in stress response and cell survival, antiapoptotic pathways are important mechanisms of bortezomib resistance. Efflux transporter P-gp was also shown to mediate a certain degree bortezomib resistance.