Targeting Neddylation Sensitizes Colorectal Cancer to Topoisomerase I Inhibitors by Inactivating the DCAF13-CRL4 Ubiquitin Ligase Complex

Investigators showed that pevonedistat blocked the ubiquitin/proteasome-dependent repair of TOP1 DNA-protein crosslinks (TOP1-DPCs) induced by TOP1 inhibitors and that the CUL4-RBX1 complex (CRL4) was a prominent ubiquitin ligase acting on TOP1-DPCs for proteasomal degradation upon auto-NEDD8 modification during replication.