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

By Chunaram Choudhary, Chanchal Kumar, Florian Gnad, M. L. Nielsen, Michael Rehman, T. Walther, Jesper V. Olsen, Matthias Mann. Science, 2009

4,055 citations recorded by the source corpus.

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.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/8e064c35b25e8682c5ca061ebb4d339e91ccf799

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Citations in the corpus

Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome. (2013, background): “Protein acetylation has emerged as a major posttranslational modification, and accumulating evidence indicates that acetylation rivals phosphorylation as a regulatory modification (Chen et al., 2012; Choudhary et al., 2009; Henriksen et al., 2012; Kim et al., 2006; Lundby et al., 2012; Pagliarini et”
SIRT3 Deficiency and Mitochondrial Protein Hyperacetylation Accelerate the Development of the Metabolic Syndrome (2011, positive): “…proteomics analyses revealed that every major metabolic pathway contains acetylated proteins, including glycolysis, the tricarboxylic acid (TCA) cycle, the urea cycle, fatty acid metabolism, and glycogen metabolism (Choudhary et al., 2009; Kim et al., 2006; Wang et al., 2010; Zhao et al., 2010).”
Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation. (2010, background): “SOD2 was identified in mass spectrometry-based screens for acetylated peptides (Choudhary et al., 2009; Kim et al., 2006, 2010; Schwer et al., 2009).”
The Roles of Post-translational Modifications in the Context of Protein Interaction Networks (2015, background): “The modulation of protein function via different types of post-translational modifications (PTMs) and their combinatorial interplay has attracted considerable attention in recent years [15–27].”
Acetylation Targets the M2 Isoform of Pyruvate Kinase for Degradation through Chaperone-Mediated Autophagy and Promotes Tumor Growth (2011, positive): “Protein acetylation has recently emerged as a broadly used modification in the regulation of a wide range of cellular processes (Choudhary et al., 2009; Kim et al., 2006; Zhao et al., Mol Cell.”
Lysine succinylation is a frequently occurring modification in prokaryotes and eukaryotes and extensively overlaps with acetylation. (2013, background): “Advances in high-resolution mass spectrometry (MS) and antibody-based affinity enrichment of acetylated lysine residues enabled the identification of thousands of acetylation sites (Choudhary et al., 2009; Kim et al., 2006), triggering a new appreciation of acetylation as a regulatory posttranslatio”
Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials (2019, background): “In addition to those included in the five groups, some new synthetic compounds also act as inhibitors of HDACs.”