Lysine Acetylation Targets Protein Complexes and Co-Regulates Major Cellular Functions

Science. 2009 Jul 16. [Epub ahead of print]

Lysine Acetylation Targets Protein Complexes and Co-Regulates Major Cellular Functions.

Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther T, Olsen JV, Mann M.

Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Martinsried, Germany.; The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.

Lysine acetylation is a reversible post-translational modification of proteins with a key role in regulating gene expression. Technological limitations have so far prevented a global analysis of its cellular roles. We used high-resolution mass spectrometry to identify 3,600 lysine acetylation sites on 1,750 proteins and quantified acetylation changes in response to the deacetylase inhibitors SAHA 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 to that of other major post-translational modifications.

http://www.ncbi.nlm.nih.gov/pubmed/