Assessment of HDACi-Induced Acetylation of Nonhistone Proteins by Mass Spectrometry

Methods Mol Biol. 2017:1510:313-327. doi: 10.1007/978-1-4939-6527-4_23.

Abstract

Posttranslational acetylation of lysine residues has been discovered as multifaceted regulatory modification for various nuclear, cytoplasmic, and mitochondrial proteins. The implementation of high-resolution and high-throughput mass spectrometry (MS) approaches has led to the identification of a hitherto underappreciated, large number of acetylation sites for a broad spectrum of cellular proteins. In this chapter, we describe a comprehensive protocol for the purification of an in vivo-acetylated, ectopically expressed, FLAG-epitope tagged nonhistone protein through immunoprecipitation (IP). The protocol also covers the sample preparation by SDS-PAGE, proteolytic digestion, and the analysis by LC-ESI MS. The success of this methodology, however, strongly depends on the physico-chemical properties of the respective protein(s) and the quality of selected peptide mass spectra.

Keywords: FLAG-tag purification; Histone deacetylase inhibitor; Immunoprecipitation; LC ESI tandem MS; Lysine acetylation; Mass spectrometry analysis; Posttranslational modification.

MeSH terms

  • Acetylation
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Electrophoresis, Polyacrylamide Gel
  • HeLa Cells
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Immunoprecipitation
  • Oligopeptides / genetics
  • Oligopeptides / metabolism
  • Protein Processing, Post-Translational*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism*
  • Spectrometry, Mass, Electrospray Ionization / methods*
  • Transfection

Substances

  • Chromosomal Proteins, Non-Histone
  • Histone Deacetylase Inhibitors
  • Oligopeptides
  • Recombinant Fusion Proteins
  • FLAG peptide