SCF activity is sustained by dynamic cycles of assembly and disassembly. (A). DNA damage checkpoint pathways feed into the proteolytic degradation of key cell cycle regulators, mediated by SCF, to stop the cell cycle. The scheme indicates the elements that make up signal transducers (ATM, ATR, Chk1, Chk2) and effectors (SCF, CSN and 26S proteasome). MIF binds to Jab1/CSN5 and prevents it from interacting with proteins targeted by CSN, notably the Cullins. (B). Multi-subunit structure of the SCF class of E3 ubiquitin ligases. All SCFs consist of Cullins, Skp1, Rbx1 and F-box proteins which associate to form an enzymatically active complex. The posttranslational modification of Cullin (Cul1) by Nedd8 renders SCF active, though unstable. The removal of Nedd8 from Cullin is catalyzed by Jab1/CSN5. Following deneddylation of Cullins, Skp1 and F-box proteins are replaced by the inhibitory protein Cand1.