Hong Kong InterUniversity Biochemistry Postgraduate Symposium 2014 

Invited Keynote Speakers

Speaker 1

Professor Daniel Finley

Dr. Finley’s laboratory published groundbreaking studies into the intricate workings of proteasome-dependent protein degradation, with a focus on the proteasome itself. The laboratory employed genetic and biochemical approaches to gain insights into the proteasome’s 35-plus component structure, the assembly, and the mechanics (both enzymatic and non-enzymatic) of this biological machine, which is critical for cellular homeostasis. These recent studies have capitalized on yeast genetics to facilitate the interrogation of proteasome activities and the cellular mechanisms that integrate the proteasome activities into the cellular metabolic equilibrium. The lab’s studies on the deubiquitinating enzyme Ubp6 (the human ortholog is Usp14) uncovered multiple activities for this tightly associated component of the proteasome. Elegant studies demonstrated that Ubp6 is adept at stalling the catabolism of ubiquitinated substrates, thus curbing proteasome activity. This activity does not involve its deubiquitinating enzymatic activity, demonstrating that Ubp6 possesses dual functions that work together to counterbalance protein degradation. The laboratory also found that Ubp6 is important for cementing the Hul5 ubiquitin ligase to the proteasome complex.Other experiments have shown that the architectural integrity of the proteasome, consisting of a regulatory and core particle, is preserved by specific molecules, as well as the process of protein degradation itself. The laboratory has also investigated proteasome activity in cells undergoing a stress response. The lab found that effective regulatory constraints are operable for maintaining proteasome levels and perturbations in ubiquitin levels, which trigger a stress response, lead to an altered composition of proteasomal subunits rather than increases in the number of proteasome complexes, as is observed following proteasome stress.