At is conjugated to the K720 residue of Cul-1 (and to an homologous lysine in all other Cullins as well) using Uba3 (E1), Ubc12 (E2), and Roc1 (E3) [28,29,30,31]. This modification is in turn cleaved off by the multisubunit COP9 Signalosome (CSN) [32,33]. Since mutations in the pathways that conjugate and remove Nedd8 are detrimental, the current model is that cycles of neddylation and de-neddylat