Nε-lysine acetylation was discovered more than half a century ago as a post-translational modification of histones and has been extensively studied in the context of transcription regulation. In the past decade, proteomic analyses have revealed that non-histone proteins are frequently acetylated and constitute a major portion of the acetylome in mammalian cells. Indeed, non-histone protein acetylation is involved in key cellular processes relevant to physiology and disease, such as gene transcription, DNA damage repair, cell division, signal transduction, protein folding, autophagy and metabolism. Acetylation affects protein functions through diverse mechanisms, including by regulating protein stability, enzymatic activity, subcellular localization and crosstalk with other post-translational modifications and by controlling protein–protein and protein–DNA interactions. In this Review, we discuss recent progress in our understanding of the scope, functional diversity and mechanisms of non-histone protein acetylation.
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The authors thank the members of their laboratory for helpful discussions. They sincerely apologize to their colleagues whose interesting work they were unable to cite owing to space constraints. C.C. is supported by the Hallas Møller Investigator Fellowship from the Novo Nordisk Foundation (NNF14OC0008541). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 648039). The Novo Nordisk Foundation Center for Protein Research is supported financially by the Novo Nordisk Foundation (grant agreement: NNF14CC0001).
Nature Reviews Molecular Cell Biology thanks M. Hirschey, Y. Zhao and the other anonymous reviewer(s) for their contribution to the peer review of this work.
A protein domain of ~110 amino acids that binds to acetylated lysine and is found in many proteins involved in transcription regulation.
- Lysine acylations
Post-translational modifications of lysine with different types of acyl-CoA, such as acetyl-CoA, butyryl-CoA, propionyl-CoA, succinyl-CoA, glutaryl-CoA and crotonyl-CoA.
- ε-Amino side chain
The amino group located on the epsilon carbon of the lysine side chain.
- Acyl stress
Cellular stress caused by the accumulation of non-enzymatic lysine acylations.
- Cornelia de Lange syndrome
A genetic developmental disorder that is characterized by reduced growth, bone abnormalities and intellectual disability.
- Tudor domain
A protein–protein interaction domain first identified in the fruitfly protein Tudor. Some Tudor domains bind to methylated lysine or arginine residues.
- Pleckstrin homology domain
(PH domain). A protein domain that is found in diverse proteins that are involved in cell signalling and cytoskeleton formation; some PH domains bind to phosphoinositides and thus recruit proteins to the plasma membrane.
- PDZ domain
A protein domain that binds to short peptide sequences in interacting proteins. Proteins with PDZ domains serve as scaffolds of multi-protein complexes, often at the cell membrane and cell–cell junctions.
A protein that assists in the folding and unfolding of client proteins and thus contributes to the assembly and disassembly of macromolecular protein complexes.
- KIX domain
A domain in the acetyltransferases CREB-binding protein (CBP) and p300 that mediates their interaction with phosphorylated CREB and other transcription regulators.
- YEATS domain
A domain in several chromatin-binding proteins; some YEATS domains bind to acetylated or crotonylated lysine.
- Double plant homeodomain
Also known as double PHD finger (DPF), a protein interaction domain that binds to acylated lysine residues.
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Nature Reviews Genetics (2019)
Scientific Reports (2019)