SUMOylation

SUMOylation is a reversible post-translational modification in which a small ubiquitin-like modifier (SUMO) is covalently attached to lysine residues on target proteins. The modification proceeds through a conserved enzymatic cascade: activation by an E1 activating enzyme (the SAE1–SAE2 heterodimer in humans), transfer to the E2 conjugating enzyme UBC9, and often assistance by an E3 ligase that provides substrate specificity, such as members of the PIAS family or RANBP2. SUMO is attached via an isopeptide bond between the SUMO C-terminus and the target lysine, and SUMO–SUMO conjugates (polySUMO chains) can also form under certain circumstances.

In humans, several SUMO paralogs exist, including SUMO-1, SUMO-2, and SUMO-3, with SUMO-4 being less well characterized. SUMO-2 and SUMO-3 are highly similar and readily form polySUMO chains, whereas SUMO-1 more often acts as a monomeric modifier and does not promote chain formation as efficiently. Processing of SUMO precursors and deconjugation from substrates are carried out by SUMO-specific proteases (SENPs), which also regulate SUMO maturation and recycling.

SUMOylation influences a broad array of cellular functions. It modulates transcription and chromatin structure, participates in DNA repair and replication, affects nuclear transport, and modulates signaling pathways. By altering protein stability, localization, activity, and interaction networks, SUMOylation acts as a dynamic regulator in cellular responses to stress and during development. Misregulation of SUMO pathways has been linked to diseases including cancer and neurodegenerative disorders, making SUMOylation a focus of biomedical research.