Fig. 3.

Summary of DUB inhibitors and their effect. a b-AP15 and WP1130 inhibit proteasomal DUBs, preventing deubiquitination at the proteasome. Blocking of deubiquitination prevents the proteasome from processing ubiquitin-tagged proteins. b P5091 inhibits USP7. Inhibition of USP7 prevents deubiquitination of HDM2, destabilizing it, which in turns stabilizes p53. p53 activates pro-apoptotic pathways, causing tumor cell death. c USP8i inhibits USP8. USP8 mediates the recycling of RTKs from the cell surface. Inhibition by USP8i may reduce surface expressed levels of RTKs, providing an alternative avenue of inhibiting oncogenic RTK signaling in EGFR inhibitor-resistant tumors