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Lysine Acetylation Targets Protein Complexes and Co-Regulates Major Cellular Functions
Chunaram Choudhary,1,2 Chanchal Kumar,1 Florian Gnad,1 Michael L. Nielsen,1,2 Michael Rehman,3 Tobias C. Walther,3 Jesper V. Olsen,1,2 Matthias Mann1,2,*
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.
1 Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Martinsried, Germany.
2 The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
3 Organelle Architecture and Dynamics, Max Planck Institute for Biochemistry, 82152 Martinsried, Germany.