Sumoylation Mechanisms in Cellular Processes

Sumoylation is a reversible post-translational modification in which members of the small ubiquitin-like modifier (SUMO) family are covalently attached to substrate proteins. This process requires an activating enzyme (E1), a conjugating enzyme (E2) and, in many cases, a ligase (E3) that confers specificity. Counteracting deSUMOylating proteases remove SUMO to restore the unmodified state. Through dynamic cycles of conjugation and deconjugation, sumoylation regulates protein localisation, complex assembly, transcription, DNA repair, cell cycle progression and stress responses. Interplay or crosstalk with other modifications, notably ubiquitylation, further refines cellular signalling pathways. Dysregulation of sumoylation can compromise genome stability, provoke inflammatory cascades or contribute to disease pathogenesis.

Research from Nature Portfolio

Recent studies have illuminated the spatial and temporal control of sumoylation in the DNA damage response. One investigation revealed that the protease SENP6 selectively removes polySUMO2/3 chains from key repair factors, such as BRCA1 and BLM, thereby ensuring timely recruitment and disassembly at DNA break sites. A complementary proteomic analysis provided the first large-scale map of endogenous SUMO2/3 modification across human cells and multiple mouse tissues, uncovering tissue-specific SUMO equilibria and substrate preferences. Further work has detailed the intimate crosstalk between SUMO and ubiquitin, showing that sequential enrichment strategies can capture over 10 000 SUMO sites alongside ubiquitylation marks, and demonstrating how SUMOylation of proteasome subunits governs their targeting to PML nuclear bodies.

Sumoylation Mechanisms in Cellular Processes publication trend

The graph below shows the total number of articles in sumoylation mechanisms in cellular processes across all publications each year (not limited to Nature Index journals).

Technical terms

SUMO: Small ubiquitin-like modifier, a family of proteins that are covalently attached to lysine residues on target proteins.

Sumoylation: Enzymatic process of conjugating SUMO to substrate proteins via E1, E2 and often E3 enzymes.

deSUMOylation: Removal of SUMO from substrates by SUMO-specific proteases to reverse modification.

E3 ligase: Enzyme that facilitates transfer of SUMO from the E2 conjugating enzyme to a specific substrate.

SUMO-interaction motif (SIM): Short hydrophobic sequence on proteins that mediates non-covalent binding to SUMO.

Crosstalk: Functional interplay between sumoylation and other post-translational modifications, such as ubiquitination.

References

1. SENP6 regulates localization and nuclear condensation of DNA damage response proteins by group deSUMOylation. Nature Communications (2023).
2. Site-specific characterization of endogenous SUMOylation across species and organs. Nature Communications (2018).
3. Uncovering the SUMOylation and ubiquitylation crosstalk in human cells using sequential peptide immunopurification. Nature Communications (2017).
4. Cbx4 SUMOylates BRD4 to regulate the expression of inflammatory cytokines in post-traumatic osteoarthritis. Experimental & Molecular Medicine (2024).
5. GPS-SUMO: a tool for the prediction of sumoylation sites and SUMO-interaction motifs. Nucleic Acids Research (2014).
6. Protein SUMOylation modification and its associations with disease. Open Biology (2017).