Cereblon-based small-molecule degraders rely on the sequential action of ubiquitin-conjugating enzymes UBE2G1 and UBE2D3 to assemble K48-linked polyubiquitin chains on cereblon neomorphic substrates, resulting in their proteasomal degradation.

Functional genomic screening reveals new synthetic lethality with and modes of resistance to epidermal growth factor receptor (EGFR) targeted therapy in EGFR-mutant human lung cancer.

Human cullin-RING ligases are buffered to a much greater extent than had been previously appreciated, and the roles of ubiquitin chain extension enzymes are far more nuanced at physiological concentrations.