Deubiquitinase-Targeting Chimeras Mediated Stabilization of Tumor Suppressive E3 Ligase Proteins as a Strategy for Cancer Therapy

a linker, we developed two series of PRO-DUBTACs─VHL-DUBTAC and KEAP1-DUBTAC─that effectively stabilize the tumor-suppressive E3 ligases VHL and KEAP1 in cells, respectively, in an OTUB1-dependent manner to retard tumor cell growth. PRO-DUBTAC could be a versatile and generalizable platform for the selective stabilization of tumor-suppressor E3 ligases, thereby opening new therapeutic avenues for targeted cancer therapies by harnessing the tumor-suppressive potential of E3 ligases.