DEUBIQUITINATING ENZYMES - A NEW CLASS OF BIOLOGICAL REGULATORS

Protein ubiquitination controls many intracellular processes, includin g cell cycle progression, transcriptional activation, and signal trans duction. Like protein phosphorylation, protein ubiquitination is dynam ic, involving enzymes that add ubiquitin (ubiquitin conjugating enzyme s) and enzymes that remove ubiquitin (deubiquitinating enzymes). Consi derable progress has been made in the understanding of ubiquitin conju gation and its role in regulating protein degradation. Recent studies have demonstrated that regulation also occurs at the level of deubiqui tination. Deubiquitinating enzymes are cysteine proteases that specifi cally cleave ubiquitin from ubiquitin-conjugated protein substrates. G enome sequencing projects have identified many candidate deubiquitinat ing enzymes, making them the largest family of enzymes in the ubiquiti n system. Deubiquitinating enzymes have significant sequence diversity and therefore may have a broad range of substrate specificities. Here we explore the structural and biochemical properties of deubiquitinat ing enzymes and their emerging roles as cellular switches.