Associate Professor, Department of Biochemistry
Equally important to protein biosynthesis is the regulated degradation of cellular proteins. Misfolding, aggregation and oxidative damage are common scenarios for the cellular protein pool. Furthermore, the correct action of many short-lived proteins involves their degradation at a precise time to terminate specific events. The major proteolytic system for the maintenance of protein homeostasis in eukaryotic cells is the ubiquitin-proteasome system (UPS). It processes up to 80 % of intracellular proteins. In consequence, impaired or overloaded UPS has been linked to a variety of human diseases such as cancer, neurodegenerative or immune system -related diseases.
The UPS consists of two collaborating modules, the ubiquitination machinery, which tags a substrate protein for degradation and the proteasome. The proteasome is one of the most complex enzymes found in cells and consists of more than 30 subunits and multiple associated proteins. Its activity is controlled at many levels to prevent unproductive protein turnover. The central building block of the proteasome is the proteolytic core cylinder (20S proteasome or core particle, CP) which needs to be activated by an associating complex, the 19S or regulatory particle, RP. Alternatively the proteasome core cylinder can interact with other proteasome activators. It is assumed that the different activators target different groups of substrates.
Our lab is interested in investigating the mechanism and function of the universally conserved proteasome activtor Blm10/PA200. Mice lacking PA200 show defective spermatogenesis and studies in our lab suggest a role for yeast Blm10-proteasomes in metabolic control. Using a broad spectrum of biochemical, cell biological and novel genome wide approaches, we anticipate to provide new insights into the mechanisms that regulate proteasome activity and to identify novel proteasome targets and cellular functions.
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Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Forchheimer Building, Room 305
Bronx, NY 10461