Project 445060

The proteasome is a tiny machine that exist in all living cells. This machine is responsible for the timely degradation of unwanted proteins, malformed proteins or proteins in surplus. This process in extremely important for cell proliferation and function. Aberrant degradation or diminished degradation of cellular proteins engender many diseases including cancer and brain pathologies. However, the exact mechanisms underlying the normal functions and disease associated alterations of the proteasome are still poorly understood. We recently discovered that, under conditions of nutrient deprivation, the proteasome complex assemble with other proteasomes and form large structures, also called bodies or foci, in the nucleus of our cells. The goal of our research is to determine why and how the proteasome orchestrates its assembly into foci. We plan to use molecular and cellular biology approaches to characterize the biological function and mechanism of action of proteasome foci. Overall, the proposed study will enhance our knowledge of the mechanisms of proteasome function in normal cells. We would also understand the defects that cause abnormal function of the proteasome in disease. Therefore, the proposed program of research would contribute to the rationale identification of targets for therapeutic interventions.