TY - JOUR T1 - An Acidic Loop and Cognate Phosphorylation Sites Define a Molecular Switch That Modulates Ubiquitin Charging Activity in Cdc34-Like Enzymes A1 - Papaleo, Elena A1 - Ranzani, Valeria A1 - Tripodi, Farida A1 - Vitriolo, Alessandro A1 - Cirulli, Claudia A1 - Fantucci, Piercarlo A1 - Alberghina, Lilia A1 - Vanoni, Marco A1 - De Gioia, Luca A1 - Coccetti, Paola Y1 - 2011/05/26 N2 - Author Summary A major mechanism for promoting protein regulation in eukaryotes involves the labeling with ubiquitin molecules of target proteins. Protein ubiquitination is involved in almost all aspects of eukaryotic cellular functions and is mediated, at the molecular level, by a hierarchical cascade of three different enzymes. Among these enzymes, E2 ubiquitin-conjugating enzymes are located at the heart of the ubiquitination pathway and are key mediators of protein ubiquitination, which strongly influence the ultimate fate of the target substrates. Since several E2s have also been related to a variety of cancer and neurodegenerative disorders, increasing efforts are being devoted to the understanding of E2 regulation at the molecular level, a mandatory step for a complete understanding of the ubiquitination process. In the present contribution, we propose, by computational and biochemical investigations, a conserved mechanism of regulation by phosphorylation of the catalytic activity of a class of E2 enzymes, which plays a major role in the regulation of cell cycle progression and tumor development. Our results shed new light on and clarify molecular aspects related to one of the first steps of the ubiquitination cascade and its regulation. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 7 IS - 5 UR - https://doi.org/10.1371/journal.pcbi.1002056 SP - e1002056 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1002056 ER -