Office: Mrb 273
Phone: (970) 492-4117
- Ph.D., University of California at Berkeley
Molecular recognition and protein-protein interactions as applied to ubiquitin biochemistry and ubiquitin-proteasome mediated protein degradation. The ubiquitin system is the major route of regulated intracellular proteolysis in all eukaryotes, and it is responsible for the control of numerous key regulatory proteins. In this pathway, proteins are modified by covalent attachment of ubiquitin, a 76-amino acid protein. Typically, multiple ubiquitins in the form of a polyubiquitin chain are elaborated from one or more lysine sidechains of the target protein. Classically, polyubiquitinated proteins are known to be recognized and degraded by the 26S proteasome, a 2.5 MDa ATP-dependent protease complex. However, depending upon the types of ubiquitin-ubiquitin linkages in the polyubiquitin chain, ubiquitination also can lead to other fates. Thus, mono- or polyubiquitin signals are used in endocytosis and protein trafficking, transcription activation, kinase activation cascades, and chromatin remodeling. Ubiquitin can be removed from conjugates through the action of various deubiquitinating enzymes (DUBs); consequently, many DUBs serve important regulatory functions. Our research is focused on three areas of ubiquitin biochemistry: (1) recognition of linkage-specific polyubiquitin conjugates, (2) the structures, mechanisms, and functions of deubiquitinating enzymes, and (3) quantitation of ubiquitin homeostasis and dynamics in living cells. Our experimental approaches range from protein biochemistry and biophysical studies to cell biology.