SUMO proteases as potential targets for cancer therapy

Abstract
Sumoylation is a post-translational protein modification that plays a crucial role in regulating various cellular processes, including DNA replication and repair, transcription, signal transduction, and nuclear transport. This process involves the covalent attachment of SUMO proteins to the ε-amino group of lysine residues in target proteins through a cascade of enzymatic reactions facilitated by E1, E2, and E3 enzymes. A key feature of sumoylation is its reversibility, which is mediated by SUMO-specific proteases known as SENPs (sentrin/SUMO-specific proteases). SENPs utilize their isopeptidase activity to catalyze the deconjugation of SUMO proteins. Additionally, these enzymes function as hydrolases in SUMO protein maturation by cleaving a short C-terminal fragment from the inactive SUMO precursor, exposing two glycine residues. SENPs help maintain the equilibrium between sumoylated and desumoylated proteins, which is essential for normal cellular function. In mammals, six SENP isoforms (SENP1, SENP2, SENP3, SENP5, SENP6, and SENP7) have been identified, categorized into three subfamilies based on their sequence TAK-981 similarity, substrate specificity, and subcellular localization. Research suggests that SUMO proteases play a role in human diseases, including cancer, highlighting their potential as targets for novel therapeutic interventions.