New insights into the role of the small ubiquitin-like modifier NEDD8/Rub1

With 58% of sequence identity and a very similar structure, NEDD8/Rub1 is the closest homologue of ubiquitin. Despite the high similarity that certifies a tight cross talk between these modifiers, ubiquitin and NEDD8/Rub1 are different: ubiquitin coordinates the modification of thousands of substrates, whereas targets of NEDD8/Rub1 are primarily members of the "cullin" family. Various studies have demonstrated that selectivity between these polypeptides caused by their E1 activating enzymes. However, it is unclear if the NEDD8/Rub1 cascade is always functionally distinct from ubiquitination. We show that unlike the very ancient origin of ubiquitin and its conserved function across all eukaryotic species, the NEDD8/Rub1 conjugation pathway appears as a dynamic adaptive machinery, whose requirement in eukaryotic cell physiology is greatly varied depending on species biology.