Dynamic S-palmitoylation of proteins controls a variety of key signaling pathways in eukaryotes that are not well understood. Our laboratory has recently developed robust chemical tools to rapidly analyze dynamic S-palmitoylation of proteins and identify S-palmitoylated proteins on large-scale. The grant application describes that application of our chemical tools to fission yeast in order to dissect the mechanisms that regulated S-palmitoylation. Our preliminary studies have revealed defects in S-palmitoylation that influence whether fission yeast cells divide (mitosis) or differentiate (meiosis). These preliminary data are very exciting as it begins to identify molecular mechanisms that eukaryotic cells use to control decision-making and cell fate and highlights the utility of Sz. pombe for mechanistic studies in S-palmitoylation. The detailed analysis of dynamic S-palmitoylation proposed in this grant is therefore essential for understanding the basic mechanisms of cell signaling and is important for dissecting the defects in protein S-palmitoylation associated with human diseases such as cancer and neurological disorders.
This proposal describes the development and application of chemical tools to fission yeast to understand fundamental mechanisms that regulate protein S-palmitoylation. These studies should reveal new pathways modulated by S-palmitoylation that are not well understood and provide important molecular insight into diseases linked to aberrant protein S-palmitoylation such as cancer and neurological disorders.
| Thinon, Emmanuelle; Fernandez, Joseph P; Molina, Henrik et al. (2018) Selective Enrichment and Direct Analysis of Protein S-Palmitoylation Sites. J Proteome Res 17:1907-1922 |
| Percher, Avital; Thinon, Emmanuelle; Hang, Howard (2017) Mass-Tag Labeling Using Acyl-PEG Exchange for the Determination of Endogenous Protein S-Fatty Acylation. Curr Protoc Protein Sci 89:14.17.1-14.17.11 |
| McMichael, Temet M; Zhang, Lizhi; Chemudupati, Mahesh et al. (2017) The palmitoyltransferase ZDHHC20 enhances interferon-induced transmembrane protein 3 (IFITM3) palmitoylation and antiviral activity. J Biol Chem 292:21517-21526 |
| Westcott, Nathan P; Fernandez, Joseph P; Molina, Henrik et al. (2017) Chemical proteomics reveals ADP-ribosylation of small GTPases during oxidative stress. Nat Chem Biol 13:302-308 |
| Thinon, Emmanuelle; Percher, Avital; Hang, Howard C (2016) Bioorthogonal Chemical Reporters for Monitoring Unsaturated Fatty-Acylated Proteins. Chembiochem 17:1800-1803 |
| Peng, Tao; Hang, Howard C (2016) Site-Specific Bioorthogonal Labeling for Fluorescence Imaging of Intracellular Proteins in Living Cells. J Am Chem Soc 138:14423-14433 |
| Percher, Avital; Ramakrishnan, Srinivasan; Thinon, Emmanuelle et al. (2016) Mass-tag labeling reveals site-specific and endogenous levels of protein S-fatty acylation. Proc Natl Acad Sci U S A 113:4302-7 |
| Peng, Tao; Thinon, Emmanuelle; Hang, Howard C (2016) Proteomic analysis of fatty-acylated proteins. Curr Opin Chem Biol 30:77-86 |
| Thinon, Emmanuelle; Hang, Howard C (2015) Chemical reporters for exploring protein acylation. Biochem Soc Trans 43:253-61 |
| Moudgil, Devinderjit K; Westcott, Nathan; Famulski, Jakub K et al. (2015) A novel role of farnesylation in targeting a mitotic checkpoint protein, human Spindly, to kinetochores. J Cell Biol 208:881-96 |
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