Biochemical characterization of cell cycle deubiquitinating enzymes

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Cell proliferation is regulated by a complex network of biochemical reactions that ensure that each cell division step is performed correctly and in proper sequence. Among these reactions is the timed degradation of cellular regulatory proteins by an enzymatic system known as the ubiquitin-proteasome system (UPS). In this system, enzyme complexes named E3 ubiquitin ligases add multiple copies of ubiquitin to a substrate protein, tagging it for rapid degradation by the proteasome. Another family of enzymes identified as deubiquitinating enzymes (DUBs) remove ubiquitin from substrate proteins, opposing the action of E3 ligases. The balance in the activities of E3 ligases and DUBs determine the stability of substrate proteins and plays a key role in the regulation of the cell division cycle. Deregulation of this balance leads to uncontrolled cell proliferation and genetic instability.