sumoylatie

Sumoylation is a reversible post-translational modification in which the small ubiquitin-like modifier SUMO is covalently attached to lysine residues on target proteins, altering their activity, stability, localization, and interactions.

The process begins with maturation of SUMO by SUMO-specific proteases (SENPs) to expose the C-terminal diglycine motif. SUMO is activated by an E1-activating enzyme (SAE1/SAE2) in an ATP-dependent reaction, then transferred to the E2-conjugating enzyme UBC9. In many cases an E3 ligase—such as members of the PIAS family or RanBP2—facilitates transfer to the substrate, increasing specificity. The conjugation forms an isopeptide bond between SUMO’s C-terminal glycine and a target lysine. The preferred site motif is ΨKxE, though non-consensus sites exist. SUMO2 and SUMO3 are capable of forming polySUMO chains; SUMO1 more often acts as a single modifier. Reversibility is provided by SENPs, which remove SUMO from substrates.

In humans, SUMO1, SUMO2, and SUMO3 are best characterized; SUMO2/3 are highly inducible by stress and readily form chains, whereas SUMO4’s function remains unclear and its expression is tissue-restricted.

Functions of sumoylation span transcriptional regulation, chromatin organization, DNA damage response, nuclear transport, and control of protein stability and signaling. It often modulates interactions by creating binding platforms for SUMO-interacting motifs and, when polySUMO chains are present, can recruit SUMO-targeted ubiquitin ligases (STUbLs) such as RNF4, linking sumoylation to ubiquitination and proteasomal degradation.

Dysregulation of sumoylation is associated with development and disease, including cancer and neurodegenerative disorders. Research tools include anti-SUMO antibodies, mass spectrometry, and genetic or pharmacological manipulation.