Metabolism, cytoskeleton and cellular signalling in the grip of protein Nε- and O-acetylation

Abstract

Acetylation of the ε-amino group of lysine residues (Nε-acetylation) is a reversible post-translational modification with the potential to rival phosphorylation. In addition to histones and many transcription factors such as p53, regulators of DNA repair, replication and recombination are subject to Nε- acetylation. This modification is also important for governing the activities of various enzymes, including histone acetyltransferases, histone deacetylases, bacterial and mammalian acetyl-CoA synthases, kinases, phosphatases, the ubiquitin ligase murine double minute 2 and the chaperonin heat shock protein 90. Furthermore, lysine acetylation occurs in cellular structure proteins such as α-tubulin, actin, cortactin and p120 catenin. Strikingly, the Yersinia outer protein YopJ promotes O-acetylation of crucial serine and threonine residues that are required for activation of the MAPK/ERK kinase and IκB kinase families, which precludes their phosphorylation and blocks signal transduction. Thus, Nε- and O-acetylation are becoming recognized as two prominent mechanisms for regulating protein functions in diverse organisms.