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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM087544-02
Application #
8118271
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Chin, Jean
Project Start
2010-08-01
Project End
2015-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
2
Fiscal Year
2011
Total Cost
$323,745
Indirect Cost
Name
Rockefeller University
Department
Biology
Type
Other Domestic Higher Education
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065
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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