We show that gain-of-function cancer mutations in the KBTBD4 E3 ligase promote neodegradation of substrates via a shape-complementarity-based mechanism, which converges with the mechanism of action of the UM171 molecular glue degrader and can be blocked by HDAC1/2 inhibitors.
- Xiaowen Xie
- Olivia Zhang
- Brian B. Liau