Damaged and misfolded proteins that cannot be repaired have to be eliminated from the cell. Failure to do so, leads to the accumulation of these proteins that will then aggregate. Protein aggregation is a hallmark of a large number of neurodegenerative pathologies including Parkinson’s and Prion diseases. The ubiquitin proteasome system pays a major role in targeting aberrant proteins for proteolysis. In this system, target proteins are first modified by the covalent attachment of ubiquitin (i.e., ubiquitylation) and then recognized and degraded by the proteasome. Using a combination of cell biology and proteomic approaches, our lab is interested in understanding how the cell recognizes misfolded proteins to target them for ubiquitylation and proteolysis.
Fang NN, Chan GT, Zhu M, Comyn SA, Persaud A, Deshaies RJ, Rotin D, Gsponer J, Mayor T. (2014) “Rsp5/Nedd4 is the main ubiquitin ligase that targets cytosolic misfolded proteins following heat stress.” Nat Cell Biol. ePub Oct 26
Ng A.H., Fang N.N., Comyn S.A., Gsponer J., Mayor T. (2013) “System-Wide Analysis Reveals Intrinsically Disordered Proteins are Prone to Ubiquitylation after Misfolding Stress.” Mol. Cell. Proteomics. 12(9):2456-67
Fang N.N., Ng A.H., Measday V., Mayor T. (2011) “Hul5 HECT ubiquitin ligase plays a major role in the ubiquitylation and turnover of cytosolic misfolded proteins.” Nat Cell Biol. 13(11):1344-52
Wilde I., Brack M., Winget J.M., Mayor T. (2011) “Proteomic characterization of aggregating proteins after the inhibition of the ubiquitin proteasome system.” J Proteome Res. 10(3):1062-72.
Gies E., Wilde I., Winget J.M., Brack M., Rotblat B., Arias Novoa C., Balgi A.D., Sorensen P.H., Roberge M., Mayor T. (2010) “Niclosamide prevents the formation of large ubiquitin-containing aggregates caused by proteasome inhibition” PLoS ONE 5(12):e14410
Winget J.M. and Mayor T. (2010) “The Diversity of Ubiquitin Recognition: Hot Spots and Varied Specificity.” Mol. Cell 38(5):627-35 PubMed