SUMO ylation

Abstract Eukaryotic cells utilise the dynamic addition and removal of SUMO, a small ubiquitin‐like modifier (UBL), to modulate protein functions, interactions and localisation. Protein SUMOylation involves a cascade of dedicated enzymes that facilitate the covalent modification of specific lysine residues on target proteins with monomers or polymers of SUMO. The cellular homeostasis of SUMOylated proteins is also regulated by SUMO proteases and SUMO‐targeted ubiquitin ligase (STUbLs). SUMO proteases cleave SUMO from modified proteins. In contrast, STUbLs ubiquitinate proteins modified with SUMO chains. Recent data suggests that ubiquitination via STUbLs effects the turnover of SUMOylated proteins as well as the spatio‐temporal composition of complexes that contain SUMO‐modified proteins. Defects in the controlled addition, removal and turnover of SUMO‐modified proteins greatly affect cellular fitness and contribute to developmental defects, cancer and protein aggregation disorders. Key Concepts SUMO encodes a small ubiquitin‐like modifier that is covalently attached to lysines in target proteins. SUMOylation, the process of SUMO conjugation to a target protein, frequently occurs on a lysine situated in a SUMOylation consensus site. SUMO conjugates can be removed from target proteins by SUMO‐specific proteases. Vertebrates express three different SUMO isoforms: SUMO1, SUMO2 and SUMO3, encoded by three different genes. SUMOs can form polymers via internal SUMOylation sites in SUMO2 and SUMO3. Several proteins can bind non‐covalently to SUMOs via SUMO interaction motifs (SIMs). A finely balanced SUMOylation/de‐SUMOylation system is required for eukaryotic life. Cross‐talk between SUMOylation and ubiquitination plays a critical in the turnover of some SUMOylated proteins as well as the spatiotemporal composition of complexes that contain SUMO‐modified proteins.