fig3

Figure 3. Classification of the cullin-RING E3 ubiquitin ligases. The general catalytic core of cullin-RING ligases (CRLs) is comprised of a RING protein and a cullin-family member, which delimits this modular category of RING ubiquitin ligase. NEDD8 (Nd8, neural precursor cell expressed developmentally down-regulated protein 8), as a ubiquitin-like modifier, efficiently activates Cullins by the covalent conjugation. Each Cullin exploits modular assembly to enroll different substrates to a general catalytic core by altering its substrate receptors. Cullin family members from different organisms recruit RING-finger proteins (Rbx1/2), adaptor proteins (SKP1 for CUL1/7, Elon B/Elon C for CUL2/5, BTB for CUL3, and DDB1 for CUL4A/B) and receptor proteins (F-box proteins for CUL1, VHL for CUL2, DCAF proteins for CUL4A/B, SOCS protein for CUL5, and FBXW8 protein for CUL7) for assembling multi-subunit complexes into ubiquitinated specific substrate proteins. However, the assembly of the CRL9 complex is ambiguous. Nd8: NEDD8; Ub: ubiquitin; CUL: cullin; SKP1: S-phase kinase-associated protein 1; VHL: von Hippel-Linda; BTB: broad complex, tramtrack, ‘bric-a-brac’; CRL: cullin RING ligase; DCAF: DDB1 CUL4 associated factor; DDB1: DNA damage-binding protein 1; RING: really interesting new gene; SOCS: suppressors of cytokine signalling.