• DOI:10.1126/science.1175371
• Corpus ID: 206520776

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

@article{Choudhary2009LysineAT,
  title={Lysine Acetylation Targets Protein Complexes and Co-Regulates Major Cellular Functions},
  author={Chunaram Choudhary and Chanchal Kumar and Florian Gnad and Michael L. Nielsen and Michael Rehman and Tobias C. Walther and Jesper V. Olsen and Matthias Mann},
  journal={Science},
  year={2009},
  volume={325},
  pages={834 - 840}
}

• Chunaram Choudhary, Chanchal Kumar, +5 authors M. Mann
• Published 14 August 2009
• Biology, Chemistry
• Science

Lysine Acetylation Catalog Covalent posttranslational modification is an essential cellular regulatory mechanism by which the activity of proteins can be controlled. Advances in mass spectrometry made it possible for Choudhary et al. (p. 834, published online 16 July) to assess the prevalence of lysine acetylation throughout the whole proteome. Acetylation is much more widespread than previously appreciated and occurs on proteins participating in all sorts of biological functions. Acetylation can influence susceptibility of proteins to phosphorylation and occurs frequently on enzymes that control the modification of other proteins by covalent ubiquitination and on proteins that form large macromolecular complexes. The findings also help to characterize the actions of lysine deacetylase inhibitors, which have shown clinical promise in treatments for cancer. A proteomic-scale analysis of protein acetylation suggests that it is an important biological regulatory mechanism. 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.