Acetylomes Emerging from Bacteria to Humans

Lysine acetylation yields AcK residues (Fig. 1a). Such modified residues were first identified in histone proteins in the late 1960s (Gershey et al. 1968). Over a decade later, AcK residues were also found to be present in nonhistone proteins, including HMG (high-mobility group) proteins (Sterner et al. 1979), a-tubulin (Piperno and

ch2 I 2

Lysine (K)


ch3 I 3





■ or 3'-O-acetyl ADP-ribose and nicotinamide


Fig. 1 Cartoon illustration of acetylation and deacetylation at a lysine residue. (a) A KAT catalyzes the transfer of the acetyl moiety (in green) from acetyl-CoA to the £-group of a lysine residue, whereas an Rpd3/Hda1 family member removes the acetyl group from an acetyl lysine residue, releasing acetate. The enzymatic activity of the Rpd3/Hda1 family members is Zn2+ dependent. (b) Deacetylation by sirtuins. Different from the Rpd3/Hda1 family of deacetylases, sirtuins are NAD+-dependent enzymes and use a catalytic mechanism that is completely different from that employed by the Rpd3/Hda1 family of deacetylases. Adapted from (Kim and Yang 2011)

Fuller 1985), and the bacterial chemotaxis regulator CheY (Barak et al. 1992; Ramakrishnan et al. 1998). In the mid-1990s, the initial KATs were identified and the subsequent candidate-based approach revealed AcKs in over a hundred proteins, many of which are transcription factors (Kouzarides 2000; Yang and Seto 2008a). In the past few years, proteomic studies have identified AcKs in thousands of eukaryotic proteins (Kim et al. 2006; Choudhary et al. 2009; Zhao et al. 2010) and hundreds of bacterial proteins (Yu et al. 2008; Zhang et al. 2009; Wang et al. 2010). It is clear now that K-acetylomes are comparable to phosphoproteomes from bacteria to humans. These proteomic studies reiterate that eukaryotic K-acetylomes are not only vital for regulating chromatin-templated nuclear processes but also play important roles in various cytoplasmic processes, including energy metabolism in mitochondria. In this way, K-acetylation has emerged as a key posttranslational modification with importance potentially comparable to other major posttranslational modifications such as phosphorylation and ubiqui-tination (Norris et al. 2009). In addition to characterization of individual acetylation events per se, it will be important to investigate how K-acetylation crosstalks with other posttranslational modifications and regulates cellular processes in a fashion coordinated according to spatiotemporal cues.

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