Fig. 1
From: Regulation of cell cycle drivers by Cullin-RING ubiquitin ligases
a Schematic representation of human cullin structural domains. Cullins are displayed by size with the smallest cullin (CUL2) on top and aligned based on their neddylation site (asterisk). CRL domain information was retrieved from InterPro (https://www.ebi.ac.uk/interpro/). CH Cullin homology domain; CR cullin repeats. CR are very flexible and may account for CRL conformation change after the activation of target substrates; CPH, CUL7, PARC, and HERC2-containing domain; APC10, a domain homologous to a sequence element termed the DOC domain and found in proteins that mediate ubiquitination reactions. b Each CRL protein complex is formed from a scaffold protein or Cullin (Cullin 1, 2, 3, 4A, 4B, 5, 7 or 9), a RING finger protein (RBX1 or RBX2), an adaptor protein (SKP1 for CRL1 and CRL7 or EloC/EloB for CRL2 and CRL5, BTB for CRL3, DDB1 for CRL4s and FBXW8 or SMU1 for CRL7) and a receptor-substrate recognition protein (F-box family for CRL1 and CRL7, VHL family member for CRL2, BTB for CRL3, DCAF family for CRL4s and SOCS family for CRL5). Approximate number of known CRL receptors for each indicated CRL. c CRL complex dynamics. Deneddylated and inactive free cullins can bind to CAND1. Cullin neddylation, which is catalyzed by a NEDD8-activating enzyme and ligase and ubiquitin-conjugating enzyme, allows cullins to interact with other CRLs when released from CAND1. Neddylation is believed to induce conformational changes in CRLs (blue arrow), which leads to their interaction with the E2-ubiquitin complex and substrate ubiquitination. Ubiquitination often leads to proteolytic degradation or substrate inactivation. Cullin neddylation is reversed by the COP9/CSN signalosome, which triggers CRL disassembly.
