SUMO proteases: from cellular functions to disease

Posttranslational modification by small ubiquitin-like modifiers (SUMOs) is critical in regulating diverse cellular processes including gene expression, cell cycle progression, genome integrity, cellular metabolism, and inflammation and immunity. The covalent attachment of SUMOs to target proteins is highly dynamic and reversible through the concerted action of SUMO conjugating and deconjugating enzymes. In mammalian cells, sentrin-specific proteases (SENPs) are the most abundant family of deconjugating enzymes. This review highlights recent advances in our knowledge of the substrates and cellular and physiological processes controlled by SENPs. Notably, SENPs are emerging as significant players in cancer, as well as in other diseases, making them attractive targets for therapeutic intervention. Consequently, a growing amount of effort in the field is being directed towards the development of SENP inhibitors.