CRL4s: the CUL4-RING E3 ubiquitin ligases

The evolutionarily conserved cullin family proteins can assemble as many as 400 distinct E3 ubiquitin ligase complexes that regulate diverse cellular pathways. CUL4, one of three founding cullins conserved from yeast to humans, uses a large β-propeller protein, DDB1, as a linker to interact with a subset of WD40 proteins that serve as substrate receptors, forming as many as 90 E3 complexes in mammals. Many CRL4 complexes are involved in chromatin regulation and are frequently hijacked by different viruses.