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. This study identifies and characterizes a novel deSUMOylase, DeSI‐1, and one of its targets, the transcriptional repressor BZEL. This is the first family of SUMO proteases to be discovered since the description of the sentrin‐specific proteases (SENPs), and they probably recognize a different set of substrates.