Profiling and inhibiting reversible palmitoylation

Curr Opin Chem Biol. 2013 Feb;17(1):20-6. doi: 10.1016/j.cbpa.2012.11.023. Epub 2013 Jan 1.


Protein palmitoylation describes the posttranslational modification of cysteines by a thioester-linked long-chain fatty acid. This modification is critical for membrane association, spatial organization, and the proper activity of hundreds of membrane-associated proteins. Palmitoylation is continuously remodeled, both by spontaneous hydrolysis and enzyme-mediated de-palmitoylation. Bioorthogonal pulse-chase labeling approaches have highlighted the role of protein thioesterases as key regulators of palmitoylation dynamics. Importantly, thioesterases are critical for regulating the spatial organization of key oncogenic proteins, such as Ras GTPases. New inhibitors, probes, and proteomics methods have put a spotlight on this emerging posttranslational modification. These tools promise to advance our understanding the enzymatic regulation of dynamic palmitoylation, and present new opportunities for drug development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Drug Discovery / methods
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Lipoylation / drug effects
  • Protein Processing, Post-Translational / drug effects
  • Proteins / metabolism*
  • Proteomics / methods*
  • Thiolester Hydrolases / antagonists & inhibitors
  • Thiolester Hydrolases / metabolism


  • Enzyme Inhibitors
  • Proteins
  • Thiolester Hydrolases