Proteomic studies on protein modification by cyclopentenone prostaglandins: expanding our view on electrophile actions

J Proteomics. 2011 Oct 19;74(11):2243-63. doi: 10.1016/j.jprot.2011.03.028. Epub 2011 Apr 1.

Abstract

Cyclopentenone prostaglandins (cyPG) are lipid mediators that participate in the mechanisms regulating inflammation and tumorigenesis. cyPG are electrophilic compounds that act mainly through the covalent modification of cellular proteins. The stability of many cyPG-protein adducts makes them suitable for proteomic analysis. Indeed, methodological advances in recent years have allowed identifying many cyPG targets, including components of pro-inflammatory transcription factors, cytoskeletal proteins, signaling kinases and proteins involved in redox control. Insight into the diversity of cyPG targets is providing a better understanding of their mechanism of action, uncovering novel links between resolution of inflammation, proliferation and redox regulation. Moreover, identification of the target residues has unveiled the selectivity of protein modification by these electrophiles, providing valuable information for potential pharmacological applications. Among the challenges ahead, the detection of proteins modified by endogenous cyPG and the quantitative aspects of the modification require further efforts. Importantly, only a few years after the appearance of the first proteomic studies, research on cyPG targets is yielding new paradigms for redox and electrophilic signaling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cyclopentanes / pharmacology*
  • Electron Transport / drug effects
  • Gastrointestinal Agents / pharmacology
  • Humans
  • Models, Biological
  • Oxidation-Reduction
  • Prostaglandins / pharmacology*
  • Protein Processing, Post-Translational / drug effects*
  • Proteins / drug effects*
  • Proteins / metabolism
  • Proteomics / methods*
  • Signal Transduction / drug effects

Substances

  • Cyclopentanes
  • Gastrointestinal Agents
  • Prostaglandins
  • Proteins
  • cyclopentenone