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Illuminating the impact of N-terminal acetylation: from protein to physiology

Nina McTiernan, Ine Kjosås, Thomas Arnesen

2025Nature Communications55 citationsDOIOpen Access PDF

Abstract

N-terminal acetylation is a highly abundant protein modification in eukaryotic cells. This modification is catalysed by N-terminal acetyltransferases acting co- or post-translationally. Here, we review the eukaryotic N-terminal acetylation machinery: the enzymes involved and their substrate specificities. We also provide an overview of the impact of N-terminal acetylation, including its effects on protein folding, subcellular targeting, protein complex formation, and protein turnover. In particular, there may be competition between N-terminal acetyltransferases and other enzymes in defining protein fate. At the organismal level, N-terminal acetylation is highly influential, and its impairment was recently linked to cardiac dysfunction and neurodegenerative diseases. N-terminal acetylation is a ubiquitous protein modification in eukaryotes. Here, the authors review the N-terminal acetylation machinery, its impact on protein function and fate, and its role in physiology and human disease.

Topics & Concepts

Terminal (telecommunication)AcetylationPosttranslational modificationPhysiologyComputational biologyChemistryBiologyCell biologyComputer scienceBiochemistryGeneTelecommunicationsEnzymePeptidase Inhibition and AnalysisUbiquitin and proteasome pathwaysSignaling Pathways in Disease