Ubiquitin-Proteasome System

The first area of focus is understanding the role of protein processing and degradation with in the endosomal/lysosomal pathway and in the cytoplasm. The lysosomal pathway is responsible for degradation of extracellular proteins within the cytoplasm and the major (and best understood) proteolytic system is the ubiquitin-proteasome system. This pathway involves dozens of distinct components and is involved in the degradation of short lived and abnormal proteins. Using eukaryotic mutants of the pathway and specific antibodies to components of the pathway, the Schwartz laboratory identified a linkage between these two systems. Furthermore, using in vitro reconstituted systems they have begun to dissect the structural elements of substrates (including oncoproteins) that signal their processing and degradation. Our recent focus is on the role of the ubiquitin-proteasome in transcription-factor (e.g., myoD, E2A) degradation in the cytoplasm and nucleus and the molecular mechanisms involved.

Receptor-Mediated Endocytosis

The second area is the cell and molecular biology of receptor-mediated endocytosis and its regulation. The Schwartz research group has identified a huge, multifunctional cell surface endocytosis receptor (LRP) which governs the plasma clearance of several physiologically important ligands including the plasminogen activators t-PA and u-PA, as well as apolipoprotein E, lipoprotein lipase and, most recently, TFPI (tissue factor pathway inhibitor), a regulator of blood coagulation. Our approaches include immuno-electron microscopy, as well as in vivo gene targeting. Recent focus is directed to regulation of LRP and ligand trafficking and turnover.


© 2020 by Washington University in St. Louis
One Brookings Drive, St. Louis, MO 63130