Linking Ubiquitin Research to Drug Discovery

January 2015: Cullin Ring Ligase (CRL) products

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The cullin-RING ubiquitin ligases (CRLs) are a superfamily of multi-component RING-E3 complexes that comprise a cullin scaffold protein and a catalytic RING subunit, Rbx1 or Rbx2. To date, seven closely related cullin proteins, Cul1, Cul2, Cul3, Cul4A, Cul4B, Cul5 and Cul7 have been identified. The cullin proteins exist in complex with Rbx1 or Rbx2 and form different subfamilies of CRLs, CRL1–CRL5 (Figure 1). The largest of these families the Skp1-Cullin1 (Cul1)-FBox Protein (FBP) (SCF) ligases, comprise an adaptor protein Skp1 which forms a bridge between Cul1 and an FBP. The FBP is responsible for binding the substrate and is referred to as the specificity factor while Rbx1 recruits ubiquitinloaded E2 conjugating enzyme which – as part of the CRL complex – enables ubiquitylation of the substrate (Bennet et al., 2010; Zimmerman et al., 2010; Lydeard et al., 2013).

  • January 2015: Cullin Ring Ligase (CRL) products