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. PROJECT NARRATIVE 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)
Type
Research Project (R01)
Project #
5R01GM087544-05
Application #
8706897
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Chin, Jean
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Rockefeller University
Department
Biology
Type
Graduate Schools
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10065
Peng, Tao; Yuan, Xiaoqiu; Hang, Howard C (2014) Turning the spotlight on protein-lipid interactions in cells. Curr Opin Chem Biol 21:144-53
Westcott, Nathan P; Hang, Howard C (2014) Chemical reporters for exploring ADP-ribosylation and AMPylation at the host-pathogen interface. Curr Opin Chem Biol 23:56-62
Zaro, Balyn W; Hang, Howard C; Pratt, Matthew R (2013) Incorporation of unnatural sugars for the identification of glycoproteins. Methods Mol Biol 951:57-67
Charron, Guillaume; Li, Melody M H; MacDonald, Margaret R et al. (2013) Prenylome profiling reveals S-farnesylation is crucial for membrane targeting and antiviral activity of ZAP long-isoform. Proc Natl Acad Sci U S A 110:11085-90
Zhang, Mingzi M; Wu, Pei-Yun Jenny; Kelly, Felice D et al. (2013) Quantitative control of protein S-palmitoylation regulates meiotic entry in fission yeast. PLoS Biol 11:e1001597
Grammel, Markus; Hang, Howard C (2013) Chemical reporters for biological discovery. Nat Chem Biol 9:475-84
Jiang, Hong; Khan, Saba; Wang, Yi et al. (2013) SIRT6 regulates TNF-* secretion through hydrolysis of long-chain fatty acyl lysine. Nature 496:110-3
Yount, Jacob S; Zhang, Mingzi M; Hang, Howard C (2013) Emerging roles for protein S-palmitoylation in immunity from chemical proteomics. Curr Opin Chem Biol 17:27-33
Yount, Jacob S; Karssemeijer, Roos A; Hang, Howard C (2012) S-palmitoylation and ubiquitination differentially regulate interferon-induced transmembrane protein 3 (IFITM3)-mediated resistance to influenza virus. J Biol Chem 287:19631-41
Hang, Howard C; Linder, Maurine E (2011) Exploring protein lipidation with chemical biology. Chem Rev 111:6341-58

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