Figure 4.

Modularity of cullin-RING E3 ligases. Cullin proteins are molecular scaffolds that assemble multi-subunit cullin-RING E3 ubiquitin ligase (CRL) complexes. The mammalian cullin protein family comprises eight members (CUL1 to CUL7 and PARC). In CRL, a cullin protein tethers both a substrate-recognition subunit, often through an adaptor protein, and the RING finger component. The cullin-organized CRL thus positions a substrate in close proximity to the RING-bound E2 ubiquitin-conjugating enzyme (not shown), which catalyzes the transfer of ubiquitin to the substrate. (a) General CRL composition. (b) Specific composition of the CRLs 1 to 7 and PARC. BTB, Bric-a-brac, Tramtrack, Broad-complex domain; DCAF, DDB1-CUL4 associated factor; DDB1, DNA damage-binding protein 1; Fbw8, F-box and WD repeat domain containing protein 8; PARC, p53-associated parkin-like cytoplasmic protein; SOCS, Suppressors of cytokine signaling; Skp1, S-phase kinase-associated protein 1; VHL-Box, von Hippel-Lindau box.