The Ubiquitin-Associated (UBA) Domain: On the Path from Prudence to Prurience

Without doubt, one of the more dramatic breakthroughs in recent cell cycle history has been the discovery that growth regulators are controlled by proteolysis. This concept blossomed within the last six or seven years, but the story really began when cyclins were discovered, soon followed by the suggestion that proteolysis events might control cell cycle transitions. Proteolytic targets that are now known include most of the cyclins, cyclin dependent kinase inhibitors, DNA replication factors, the securin class of proteins that inhibit loss of sister chromatid cohesion following DNA replication and, of course, the cohesion factor itself. Protein degradation is controlled in various ways including ubiquitin-dependent targeting to proteasomes, activation of ubiquitin ligases by ubiquitin-like molecule conjugation, phosphorylation of proteolytic targets, and activation of the separin class of proteases.