Regulation of Protein Function by SUMO Modification

SUMOylation is a post-translational modification that affects a large number of proteins, many of which are nuclear. While the role of SUMOylation is beginning to be elucidated, it is clear that understanding the mechanisms that regulate the process is likely to be important. Control of the levels of SUMOylation is brought about through a balance of conjugating and deconjugating activities, i.e. of SUMO (small ubiquitin-related modifier) conjugators and ligases versus SUMO proteases. Although conjugation of SUMO to proteins can occur in the absence of a SUMO ligase, it is apparent that SUMO ligases facilitate the SUMOylation of specific subsets of proteins. Two SUMO ligases in Schizosaccharomyces pombe, Pli1 and Nse2, have been identified, both of which have roles in genome stability. We report here on a comparison between the properties of the two proteins and discuss potential roles for the proteins. Introduction The mechanisms involved in the post-translational modification of proteins by SUMOylation resemble those associated with ubiquitination. However, there are a number of significant differences in the two processes. SUMO (small ubiquitin-related modifier), like ubiquitin, is produced as a precursor protein that is processed to the mature form to reveal a double glycine (-GG) motif. It is then activated by a SUMO activator (which is heterodimeric, unlike the ubiquitin activator that consists of a single protein), and then passed to a SUMO conjugator (E2), of which there is only one, unlike the case with ubiquitination, where there are several E2s. However, perhaps the most striking difference is in the requirement for a SUMO ligase. While there are