Upon their synthesis, it is imperative that proteins adopt their functional, native conformations. Proteins called molecular chaperones act to facilitate the rapid and efficient folding of proteins. Some proteins, however, due to mutation or modification, are unable to attain a functional folded state. These misfolded proteins may be deleterious to the cell and are thus targeted for degradation. In recent years, molecular chaperones have been implicated in the degradation of misfolded proteins, but their precise function remains unclear. The goal of this project is to use the yeast Saccharomyces cerevisiae as a model organism to explore misfolded protein degradation and the role that molecular chaperones play in this process. Wild-type and tumor-derived mutants of the von Hippel-Lindau (VHL) tumor suppressor protein, a known chaperone substrate, will be used as model proteins. The use of VHL to study this problem may result in new targets for therapeutic intervention in VHL-related cancers.
| McClellan, Amie J; Xia, Yu; Deutschbauer, Adam M et al. (2007) Diverse cellular functions of the Hsp90 molecular chaperone uncovered using systems approaches. Cell 131:121-35 |
| McClellan, Amie J; Scott, Melissa D; Frydman, Judith (2005) Folding and quality control of the VHL tumor suppressor proceed through distinct chaperone pathways. Cell 121:739-48 |
| Melville, Mark W; McClellan, Amie J; Meyer, Anne S et al. (2003) The Hsp70 and TRiC/CCT chaperone systems cooperate in vivo to assemble the von Hippel-Lindau tumor suppressor complex. Mol Cell Biol 23:3141-51 |
