Office: Mrb 273
Phone: (970) 492-4117
Website: http://yaocohenlab.bmb.colostate.edu
Education
- Ph.D., University of California at Berkeley
About
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.
Publications
- High-affinity free ubiquitin sensors for quantifying ubiquitin homeostasis and deubiquitinationNature Methods 16: 771–777, 2019
- Structural basis for the activation and inhibition of the UCH37 deubiquitylaseMolecular Cell 57: 901-911, 2015
- Mixed-linkage ubiquitin chains send mixed messagesStructure 21: 727-740, 2013
- Polyubiquitin-sensor proteins reveal localization and linkage-type dependence of cellular ubiquitin signalingNature Methods 9: 303–309, 2009
- Linkage-Specific Avidity Defines the Lysine 63-Linked Polyubiquitin-Binding Preference of Rap80Molecular Cell 33: 775-783, 2009
- Avid interactions underlie the Lys63-linked polyubiquitin binding specificities observed for UBA domainsNature Structural & Molecular Biology 16: 883–889, 2009
- Specificity of the BRISC Deubiquitinating Enzyme Is Not Due to Selective Binding to Lys63-linked PolyubiquitinJ Biol Chem. 285: 10344-10352, 2010
- K63?specific deubiquitination by two JAMM/MPN+ complexes: BRISC?associated Brcc36 and proteasomal Poh1EMBO J 28: 621-631, 2009
- Evidence for bidentate substrate binding as the basis for the K48 linkage specificity of otubain 1J Mol Biol. 386: 1011-1023, 2009