Current Research
Protein degradation mediated by ubiquitination plays an important role in many cellular processes, particularly during cell cycle transitions. For example, the Anaphase Promoting Complex (APC) ubiquitinates a series of important cell cycle regulators during mitosis and G1 phase, orchestrating the proper segregation of chromosomes, mitotic exit and maintenance of the G1 phase. Degradation of the APC substrates is triggered by the ubiquitin conjugates that are assembled on these proteins by the APC. While recent studies suggest that these conjugates could have a complicated morphology, the question of how these conjugates are assembled by APC from a mechanistic point of view has remained elusive. Using an in vitro system, I am trying to understand how the APC assembles multiple ubiquitins on a substrate and how different ubiquitin signals contribute to the process of protein degradation by the proteasome.