Acetylation and Its Enzymes Overview and New Developments

Juliette Adjo Aka, Go-Woon Kim, and Xiang-Jiao Yang

Contents

1 K-Acetylomes Emerging from Bacteria to Humans 2

2 Three Superfamilies of KATs 3

3 Two Superfamilies of HDACs 4

4 Bromodomains, PHD Fingers, and Potentially Others for AcK Recognition 6

5 Modulation of K-Acetylation for Drug Development 7

6 K-Acetylation Modulation for Cell Reprogramming and Regenerative Medicine 8

7 Conclusion 9

References 9

Abstract Lysine (K) acetylation refers to transfer of the acetyl moiety from acetyl-CoA to the e-amino group of a lysine residue. This is posttranslational and reversible, with its level dynamically maintained by lysine acetyltransferases (KATs) and deacetylases (KDACs). Traditionally, eukaryotic KDACs have been referred to as HDACs (histone deacetylases). Recent proteomic studies have revealed that hundreds of bacterial proteins and thousands of eukaryotic proteins contain acetyl-lysine (AcK) residues, indicating that K-acetylomes are comparable to phospho-proteomes. The current challenges are to assign enzymes that execute specific acetylation events, to determine the impact of these events, and to relate this modification to other posttranslational modifications, cell signaling networks, and pathophysiology under different cellular and developmental contexts. In this chapter, we provide a brief overview about the acetylomes, KATs, HDACs,

The Rosalind & Morris Goodman Cancer Research Center, McGill University, Montreal, QC, Canada H3A 1A3

Department of Medicine, McGill University Health Center, McGill University, Montreal, QC, Canada H3A 1A3

Department of Anatomy & Cell Biology, McGill University, Montreal, QC, Canada H3A 1A3 Department of Biochemistry, McGill University, Montreal, QC, Canada H3A 1A3 e-mail: [email protected]

T.-P. Yao and E. Seto (eds.), Histone Deacetylases: the Biology and Clinical Implication, 1 Handbook of Experimental Pharmacology 206, DOI 10.1007/978-3-642-21631-2_1, © Springer-Verlag Berlin Heidelberg 2011

AcK-recognizing protein domains, and acetylation-modulating therapeutics, and emphasize the latest developments in related areas. The remaining chapters of the book focus on and cover various aspects of HDACs (both the Rpd3/Hda1 and sirtuin families), which shall provide novel insights into how to utilize these enzymes for developing a new generation of HDAC-related therapeutics.

Keywords Bromodomain • HAT • HDAC • Lysine acetylation • Lysine acetyltransferase • Lysine deacetylase • Post-translational modification

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