López Jeffrey E, Sullivan Eric D, Fierke Carol A
Interdepartmental Program in Chemical Biology, University of Michigan , 210 Washtenaw Avenue, Ann Arbor, Michigan 48109-2216, United States.
Departments of Chemistry and Biological Chemistry, University of Michigan , 930 North University Avenue, Ann Arbor, Michigan 48109-2216, United States.
ACS Chem Biol. 2016 Mar 18;11(3):706-16. doi: 10.1021/acschembio.5b01067.
Epigenetic regulation is a key factor in cellular homeostasis. Post-translational modifications (PTMs) are a central focus of this regulation as they function as signaling markers within the cell. Lysine acetylation is a dynamic, reversible PTM that has garnered recent attention due to alterations in various types of cancer. Acetylation levels are regulated by two opposing enzyme families: lysine acetyltransferases (KATs) and histone deacetylases (HDACs). HDACs are key players in epigenetic regulation and have a role in the silencing of tumor suppressor genes. The dynamic equilibrium of acetylation makes HDACs attractive targets for drug therapy. However, substrate selectivity and biological function of HDAC isozymes is poorly understood. This review outlines the current understanding of the roles and specific epigenetic interactions of the metal-dependent HDACs in addition to their roles in cancer.
表观遗传调控是细胞稳态的关键因素。翻译后修饰（PTMs）是这种调控的核心焦点，因为它们在细胞内充当信号标记。赖氨酸乙酰化是一种动态、可逆的PTM，由于其在各种癌症中的改变，最近受到了关注。乙酰化水平由两个相互对立的酶家族调节：赖氨酸乙酰转移酶（KATs）和组蛋白脱乙酰酶（HDACs）。HDACs是表观遗传调控的关键参与者，在肿瘤抑制基因的沉默中发挥作用。乙酰化的动态平衡使HDACs成为药物治疗的有吸引力的靶点。然而，HDAC同工酶的底物选择性和生物学功能了解甚少。本综述概述了目前对金属依赖性HDACs的作用、特定表观遗传相互作用及其在癌症中的作用的理解。
