DeSUMOylating isopeptidase: a second class of SUMO protease

The modification of proteins by small ubiquitin-like modifier (SUMO) is crucial for the regulation of diverse cellular processes. Protein SUMOylation is reversed by isopeptidases, collectively known as deSUMOylases. Only one family of SUMO-specific proteases has been described so far: the sentrin-specific proteases (SENP). Here, we identify and characterize a new deSUMOylase, which we have named DeSI-1 (DeSumoylating Isopeptidase 1). We describe BZEL—a new transcriptional repressor—as substrate of DeSI-1. DeSI-1 catalyses the deSUMOylation, but not the deubiquitination, of BZEL. Furthermore, the SENP substrates PML and ΔNp63 are not deSUMOylated by DeSI-1, suggesting that SENP and DeSI enzymes recognize different sets of substrates. Together, these data identify a second class of SUMO proteases.