The new landscape of protein ubiquitination

Recently developed technologies allow proteome-wide quantification of ubiquitination sites and provide avenues for identifying targets of ubiquitin ligases. Many properties of proteins, such as their stability, localization, binding partners, and their activity, can be regulated by ubiquitination, a post-translational modification (PTM) involving the transfer of ubiquitin, a 76-amino acid protein, to lysine residues1. Ubiquitin is targeted to specific proteins by E3 ligases, each of which catalyzes the transfer of ubiquitin to specific protein targets. With over 500 E3 ligases encoded in the human genome2, the complexity of the cellular machinery devoted to ubiquitination rivals phosphorylation, which is regulated by a comparably large network of kinases and phosphates. However, the number of known ubiquitination sites is markedly fewer than that of phosphorylation sites, largely due to the lack of technical approaches to profile the sites of ubiquitination across the proteome. Three recently published papers in Molecular Cell3, Molecular Cellular Proteomics4, and Cell5 have largely remedied this, providing a comprehensive view of the ubiquitinome and revealing functional consequences of ubiquitination for a large subset o