Lysine acetylation targets protein complexes and co-regulates major cellular functions

Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16.

Abstract

Lysine acetylation is a reversible posttranslational modification of proteins and plays a key role in regulating gene expression. Technological limitations have so far prevented a global analysis of lysine acetylation's cellular roles. We used high-resolution mass spectrometry to identify 3600 lysine acetylation sites on 1750 proteins and quantified acetylation changes in response to the deacetylase inhibitors suberoylanilide hydroxamic acid and MS-275. Lysine acetylation preferentially targets large macromolecular complexes involved in diverse cellular processes, such as chromatin remodeling, cell cycle, splicing, nuclear transport, and actin nucleation. Acetylation impaired phosphorylation-dependent interactions of 14-3-3 and regulated the yeast cyclin-dependent kinase Cdc28. Our data demonstrate that the regulatory scope of lysine acetylation is broad and comparable with that of other major posttranslational modifications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Amino Acid Motifs
  • Benzamides / pharmacology
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cell Physiological Phenomena*
  • Cytoplasm / metabolism
  • Enzyme Inhibitors / pharmacology
  • Histone Deacetylase Inhibitors
  • Histone Deacetylases / metabolism
  • Humans
  • Hydroxamic Acids / pharmacology
  • Lysine / metabolism*
  • Mass Spectrometry
  • Metabolic Networks and Pathways
  • Mitochondria / metabolism
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism*
  • Protein Processing, Post-Translational*
  • Protein Structure, Tertiary
  • Proteins / chemistry
  • Proteins / metabolism*
  • Proteome / analysis*
  • Proteomics
  • Pyridines / pharmacology
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism
  • Vorinostat

Substances

  • Benzamides
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Multiprotein Complexes
  • Proteins
  • Proteome
  • Pyridines
  • Saccharomyces cerevisiae Proteins
  • entinostat
  • Vorinostat
  • Histone Deacetylases
  • Lysine