Proteasome Regulation Through Activators and Inhibitors

Elisabeth Smiley*, David Smith and Taylor Thomas, Health Science Center North, West Virginia University, Morgantown, WV, 26505

Field (Broad Category): Biochemistry (Biological & Biochemical Sciences) 

Student’s Major: Biology 

Proteasomes are protein complexes that break down proteins that are no longer necessary and that functions similar to a machine, where activators increase its activity and inhibitors slow down its activity. A protein will go into the proteasome through a gate, and then molecular scissors cut the protein into small particles or pieces, and then what is left over comes out of the other end of the proteasome. When it is not working properly, it can lead to significant illnesses. Some examples of this would be neurodegenerative diseases such as Parkinson's, Alzheimer's, and Huntington's disease, as well as cancer. A nuclear proteasome activator, PA28y, has been shown to be overexpressed in some cancers and underexpressed in some neurodegenerative diseases. The implications of disease progression in relation to the function of the PA28y proteasome interaction is not well established. It is still uncertain how this interaction influences the gate of the proteasome or its proteolytic regulatory mechanism. This project tested the effect of multiple substrates with and without proteasome inhibitors on proteasomal activity, with a specific focus on the 20s proteasome through fluorescence. Excitation and emission of fluorescence molecules to gauge how specific PA28y regulates substrate breakdown via the proteasome was used. 

Funding: National Institute of Health 

Program/mechanism supporting research/creative efforts: WVU's Research Apprenticeship Program (RAP) & accompanying HONR 297-level course