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