New Proteases in a Ubiquitin Stew

Abstract

Proteins destined for degradation in the cell's garbage disposal unit, the proteasome, must first receive a ubiquitin tag. In his Perspective, Hochstrasser discusses new work (Verma et al., Cope et al.) that reveals the vital link between removal of the ubiquitin tag in the proteasome and degradation of the targeted protein. Proteins are deubiquitinated in the proteasome by a zinc-dependent metalloprotease, and protein degradation cannot take place in the absence of this enzyme.