SUMOconjugation

SUMO conjugation, also known as SUMOylation, is a reversible post-translational modification in which small ubiquitin-like modifier (SUMO) proteins are covalently attached to lysine residues on target proteins. This modification can alter protein activity, interactions, stability, and subcellular localization, thereby influencing a wide range of cellular processes.

The conjugation process follows a enzymatic cascade. SUMO precursors are matured by SUMO-specific proteases, which expose a C-terminal di-glycine motif. The mature SUMO is activated by the E1 activating enzyme complex SAE1/SAE2 in an ATP-dependent step, transferred to the E2 conjugating enzyme Ubc9, and then conjugated to substrates. E3 ligases, such as members of the PIAS family or RanBP2, help specify substrates and enhance transfer efficiency, though Ubc9 can mediate some SUMO attachment directly. Sumoylation is reversible, with SUMO-specific proteases (SENPs) removing SUMO from substrates and processing SUMO precursors.

Humans express several SUMO paralogs, with SUMO1 and SUMO2/3 being the most prominent. SUMO2 and SUMO3 are highly similar and more prone to forming polySUMO chains, whereas SUMO1 is less chain-competent. SUMO4 and SUMO5 have more limited or tissue-specific roles, and their functions are less well understood. Target proteins include transcription factors, chromatin regulators, DNA repair proteins, and components of various signaling pathways. While many SUMO attachment sites fit a consensus motif (a hydrophobic residue, a lysine, any amino acid, glutamate), numerous substrates carry non-consensus modification as well.

Sumoylation integrates with other post-translational modifications and modulates cellular responses to stress, cell cycle progression, and DNA repair, contributing to the dynamic regulation of protein function in health and disease.