deSUMOylates

DeSUMOylation is the enzymatic removal of SUMO from target proteins. SUMOylation, the attachment of the Small Ubiquitin-like Modifier (SUMO) to lysine residues, regulates protein activity, interactions, localization, and stability. DeSUMOylases reverse this modification, enabling dynamic control of cellular processes.

The removal is catalyzed by SUMO-specific proteases, which cleave the isopeptide bond linking SUMO to the substrate. In addition, many deSUMOylases process immature SUMO precursors to generate mature SUMO for conjugation. Some enzymes also disassemble SUMO chains, altering multi-SUMO signaling.

In humans, the major deSUMOylases are the SENP family (SENP1–SENP7) and the SUMO-specific protease USPL1. Yeast use Ulp1 and Ulp2, functional counterparts. These proteases differ in substrate preference (some favor SUMO1, others SUMO2/3), subcellular localization, and the ability to edit poly-SUMO chains versus single SUMO modifications.

Biological roles include regulation of transcription, chromatin structure, DNA damage response, cell cycle progression, and signaling pathways. The activity of deSUMOylases is typically responsive to cellular conditions such as stress, enabling rapid remodeling of SUMOylation states.

Dysregulation of deSUMOylation has been linked to diseases including cancer and neurodegenerative disorders. Because deSUMOylases control many essential processes, they are studied as potential targets for therapeutic intervention, with research focusing on selective inhibitors and modulators.