The CUL4 paralogs CUL4A and CUL4B assemble into structurally similar multisubunit ubiquitin E3 ligases (CRL4A/B) that regulate diverse aspects of cell biology. New work in this issue of The EMBO Journal shows that the longer N-terminal tail of CUL4B tells these molecular twins apart, by promoting the formation of paralog-specific CRL4B complexes that control cytoskeletal processes during mitosis and brain development.
© 2023 The Authors.