SUMO proteases: from cellular functions to disease.

In recent years, more substrates and cellular and physiological processes under the control of sentrin-specific proteases (SENPs) have been revealed. SENPs play important roles in gene expression, cell cycle progression, genome stability, cellular metabolism, macromolecular assemblies, and infection and immunity. SENPs have emerged as important players in tumorigenesis and as potential therapeutic targets in cancer. SENPs are frequently overexpressed in cancer and are associated with poor prognosis and resistance against anticancer drugs. Besides cancer, the dysregulation of SENPs has been linked to other diseases, including cardiac, metabolic, muscular, and neurological conditions. Because of their therapeutic potential in cancer and other diseases, increasing effort has been put into the discovery and development of SENP inhibitors. 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. [ABSTRACT FROM AUTHOR]