title: Global profiling of dynamic protein palmitoylation.
abstract: The reversible thioester linkage of palmitic acid on cysteines, known as protein S-palmitoylation, facilitates the membrane association and proper subcellular localization of proteins. Here we report the metabolic incorporation of the palmitic acid analog 17-octadecynoic acid (17-ODYA) in combination with stable-isotope labeling with amino acids in cell culture (SILAC) and pulse-chase methods to generate a global quantitative map of dynamic protein palmitoylation events in cells. We distinguished stably palmitoylated proteins from those that turn over rapidly. Treatment with a serine lipase-selective inhibitor identified a pool of dynamically palmitoylated proteins regulated by palmitoyl-protein thioesterases. This subset was enriched in oncoproteins and other proteins linked to aberrant cell growth, migration and cancer. Our method provides a straightforward way to characterize global palmitoylation dynamics in cells and confirms enzyme-mediated depalmitoylation as a critical regulatory mechanism for a specific subset of rapidly cycling palmitoylated proteins.
authors: The Department of Chemical Physiology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA.
authors: Brent R
authors: BR
authors: Martin
authors: Chu
authors: C
authors: Wang
authors: Alexander
authors: A
authors: Adibekian
authors: Sarah E
authors: SE
authors: Tully
authors: Benjamin F
authors: BF
authors: Cravatt
mesh_terms: D000818:Animals; D003545:Cysteine / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D008049:Lipase / Q000037:antagonists & inhibitors; D054878:Lipoylation / Q000187:drug effects; D013058:Mass Spectrometry; D051379:Mice; D063065:Organophosphonates / Q000494:pharmacology; D019308:Palmitic Acid / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012697:Serine Endopeptidases / Q000378:metabolism; D013869:Thiolester Hydrolases / Q000378:metabolism
chemical_list: D005231:Fatty Acids, Unsaturated; D063065:Organophosphonates; D019308:Palmitic Acid; C047008:17-octadecynoic acid; D008049:Lipase; D013869:Thiolester Hydrolases; C095299:palmitoyl-protein thioesterase; D012697:Serine Endopeptidases; D003545:Cysteine