Lysine acetylation targets protein complexes and co-regulates major cellular functions.
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.
Choudhary
Chunaram
C
Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Martinsried, Germany.
Kumar
Chanchal
C
Gnad
Florian
F
Nielsen
Michael L
ML
Rehman
Michael
M
Walther
Tobias C
TC
Olsen
Jesper V
JV
Mann
Matthias
M
D000107:Acetylation; D020816:Amino Acid Motifs; D001549:Benzamides / Q000494:pharmacology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002468:Cell Physiological Phenomena; D003593:Cytoplasm / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008239:Lysine / Q000378:metabolism*; D013058:Mass Spectrometry; D053858:Metabolic Networks and Pathways; D008928:Mitochondria / Q000378:metabolism; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D011725:Pyridines / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D000077337:Vorinostat
D001549:Benzamides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D046912:Multiprotein Complexes; D011506:Proteins; D020543:Proteome; D011725:Pyridines; D029701:Saccharomyces cerevisiae Proteins; C118739:entinostat; D000077337:Vorinostat; D006655:Histone Deacetylases; D008239:Lysine