Ubiquitin-like proteins NEDD8 is covalently attached to lysines in substrate proteins by a series of enzymatic reactions similar to those involved in ubiquitination including the E1 (NAE1/UBA3) reaction.The well-characterized substrates of NEDD8 modification (officially named as neddylation) are cullins.Regulation of NF-kappa B, a transcription factor required for the inducible expression of various proinflammatory cytokines, occurs through phosphorylation-dependent ubiquitination of IkappaB alpha, which is subsequently degraded by the 26S proteasome.