A WLM Protein with SUMO-Directed Protease Activity

Abstract

Covalent modification of eukaryotic proteins by ubiquitin and the distantly related ubiquitin-like protein called SUMO contributes to an extraordinary assortment of biological regulatory mechanisms (2). These attachments have different consequences, depending not only on which of the proteins is attached but also on whether they are in the form of a polymer. Polyubiquitin chains connected by amide (isopeptide) bonds involving certain ubiquitin lysine side chains, for instance, are often signals for directing a substrate to the proteasome for degradation. The ubiquitylation and sumoylation pathways intersect in a variety of ways. An intriguing example is the recently unearthed group of ubiquitin-ligating enzymes called SUMO-targeted ubiquitin ligases (STUbLs), which recognize (poly)SUMO-modified proteins and attach ubiquitin to the conjugates, leading to their degradation by the proteasome (3, 9). Discovery of the STUbLs has raised many interesting questions, such as whether the ubiquitin is attached to the SUMO moiety or the substrate itself in the SUMO-substrate conjugate and how SUMO and ubiquitin are recycled from these conjugates once they have reached the proteasome. In this issue, the study by Mullen et al. (8) throws fresh light on these questions through the characterization of an unusual SUMO-directed protease that may associate with the proteasome and seems able to cleave both ubiquitin and SUMO from proteins.