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.

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.