Concepts in sumoylation: a decade on

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Abstract
SUMO (small ubiquitin-related modifier) proteins are ∼10-kD polypeptides that function as reversible post-translational protein modifiers. They form isopeptide bonds with ɛ-amino groups of acceptor Lys residues in hundreds of target proteins in a process termed sumoylation. Sumoylation requires a cascade of enzymatic steps that involves an E1 activating enzyme, an E2 conjugating enzyme and, in most cases, an E3 SUMO ligase. Owing to SUMO-specific isopeptidases, this modification is highly dynamic. Acceptor Lys residues in target proteins are frequently found in the consensus motif ΨKxE (in which Ψ is a branched aliphatic amino acid and x is any amino acid), although the number of targets with non-consensus acceptor sites is steadily increasing. Sumoylation alters the molecular interactions of modified target proteins by masking or adding interaction surfaces. Downstream consequences, which are target dependent, include changes in localization, activity and protein stability. A short non-covalent SUMO-interaction/binding motif (SIM/SBM) has been identified in selected SUMO enzymes, targets and downstream effectors. This motif contributes to the mechanism and consequences of sumoylation. Reversible sumoylation contributes to many distinct pathways, such as chromatin structure, DNA repair, transcription, cell-cycle progression and trafficking. Targets can be found in the nucleus, the cytoplasm, the plasma membrane and organelles such as the endoplasmic reticulum and mitochondria.