Nat. Struct. Mol. Biol. doi:10.1038/nsmb.2890

The reversible attachment of small ubiquitin-like modifier (SUMO) proteins to the lysine side chains of specific proteins is necessary for genome stability and transcription. Whereas the ubiquitination of a protein frequently leads to its degradation, SUMOylation alters the biological function of the target protein by enabling it to interact with new protein partners. Hendriks et al. have now used high-resolution MS to identify >4,300 SUMOylation sites in >1,600 proteins in human cells. Although MS has been used to identify SUMOylation sites in cells before, these authors used a new purification strategy that was able to find these sites more efficiently. Most (∼64%) of the identified proteins had only one or two SUMO groups, but the authors identified 96 proteins that were functionalized with ten or more SUMOs. Analysis of their dataset revealed that SUMOs and other post-translational modifications (PTMs) may compete for the same lysine side chains, as ∼22% of SUMOylation sites were known ubiquitination sites, and SUMOylation also occurred at known acetylation and methylation sites. As expected, SUMOylation was found almost exclusively on nuclear or chromatin-associated proteins, with proteins involved in nucleic acid metabolism, nucleosome organization and transcription being the most common substrates. Validation of these >3,000 new putative SUMOylation sites should reveal how the attachment and removal of this PTM is able to alter the functions of proteins involved in so many different biological processes.