Genetic experiments have established an important role for the ubiquitin-like 
molecule NEDD8 (neural-precursor-cell-expressed developmentally down-regulated 
8) in the regulation of cell growth, viability and development. It is therefore 
essential to identify the molecular targets for the pathway. Until recently, the 
cullin family of proteins was characterized as the only substrates for 
NEDDylation. However, through either direct biological approaches or the use of 
proteomics, it is now evident that the NEDD8 proteome is more diverse than 
thought previously. The present review describes the biological significance of 
NEDDylation for the novel identified substrates and the emerging evidence for 
the co-operation between the ubiquitin and NEDD8 pathways to control protein 
function.