Abstract
As a type of protein post-translational modification, SUMOylation is the process that attaches a small ubiquitin-like modifier (SUMO) to lysine residues of protein substrates. Not only do SUMO and ubiquitin exhibit structure similarity, but the enzymatic cascades for SUMOylation and ubiquitination are also similar. It is well established that protein ubiquitination triggers proteasomal degradation, but the function of SUMOylation remains poorly understood compared to ubiquitination. Recent studies reveal the role of SUMOylation in regulating protein localization, stability, and interaction networks. SUMO can be covalently attached to substrates either as an individual monomer (monoSUMOylation) or as a polymeric SUMO chain (polySUMOylation). Strikingly, mono- and polySUMOylation likely play distinct roles in protein subcellular localization and the assembly/disassembly of biomolecular condensates, which are membraneless cellular compartments with concentrated biomolecules. In this review, we summarize the recent advances in the understanding of the function and regulation of SUMOylation, which could reveal potential therapeutic targets in disease pathogenesis.