Figure S19 from HDAC6 Inhibition Releases HR23B to Activate Proteasomes, Expand the Tumor Immunopeptidome and Amplify T-cell Antimyeloma Activity

Fig. S19. Graphical representation to depict the effect of HDAC6 inhibitors on proteasome activity. HDAC6 inhibitors release HR23B which is bound to the HDAC6 BUZ domain. Free HR23B binds and shuttles ubiquitinated cargo proteins to the proteasome. Rad23 binds the proteasome through a UbL (ubiquitin-like) domain and contains UBA (ubiquitin-associated) motifs that bind multi-ubiquitin chains. These domains allow Rad23 to function as a substrate shuttle-factor. Shown is the association of HR23B with the 26S proteasome through interaction with the non-ATPase regulatory subunit 14, also known as Rpn11. The ability of HDAC6 to downregulate HR23B occurs independently of its deacetylase activity.