Neddylation

Neddylation (also NEDDylation) is the process by which the ubiquitin-like protein NEDD8 is conjugated to its target proteins. This process is analogous to ubiquitination, although it relies on its own enzymes.^[1] It is an enzymatic cascade catalyzed by first UBA3 and NAE1, which form the NEDD8 activation enzyme (E1), then the NEDD8 conjugating enzyme UBE2M or UBE2F (E2), and finally the NEDD8 ligase E3, which will bind the substrate NEDD8 to the target protein. The target protein will then have its activity, localization and/or stability affected. Proteins targeted by neddylation can be largely divided into two groups: cullins and non-cullins. Cullins, when neddylated, release CAND1 from its inhibitory binding, and that leads to the activation of Cullin Ring Ligases, which in turn perform ubiquitination.