Aka Juliette Adjo, Kim Go-Woon, Yang Xiang-Jiao
The Rosalind & Morris Goodman Cancer Research Center, McGill University, Montréal, QC, Canada.
Handb Exp Pharmacol. 2011;206:1-12. doi: 10.1007/978-3-642-21631-2_1.
Lysine (K) acetylation refers to transfer of the acetyl moiety from acetyl-CoA to the ε-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 phosphoproteomes. 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, 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.
赖氨酸（K）乙酰化是指将乙酰基部分从乙酰辅酶A转移至赖氨酸残基的ε-氨基上。这是一种翻译后修饰且具有可逆性，其水平由赖氨酸乙酰转移酶（KATs）和去乙酰化酶（KDACs）动态维持。传统上，真核生物的KDACs被称为组蛋白去乙酰化酶（HDACs）。最近的蛋白质组学研究表明，数百种细菌蛋白和数千种真核生物蛋白含有乙酰赖氨酸（AcK）残基，这表明赖氨酸乙酰化组与磷酸化蛋白质组具有可比性。当前面临的挑战是确定执行特定乙酰化事件的酶，确定这些事件的影响，并将这种修饰与其他翻译后修饰、细胞信号网络以及不同细胞和发育背景下的病理生理学联系起来。在本章中，我们简要概述了乙酰化组、KATs、HDACs、AcK识别蛋白结构域以及乙酰化调节疗法，并强调了相关领域的最新进展。本书其余章节重点关注并涵盖了HDACs（Rpd3/Hda1和沉默调节蛋白家族）的各个方面，这将为如何利用这些酶开发新一代HDAC相关疗法提供新的见解。
