UCIBIO/REQUIMTE, BioSIM - Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.
Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.
Int J Mol Sci. 2020 Nov 15;21(22):8609. doi: 10.3390/ijms21228609.
The protein acetylation of either the α-amino groups of amino-terminal residues or of internal lysine or cysteine residues is one of the major posttranslational protein modifications that occur in the cell with repercussions at the protein as well as at the metabolome level. The lysine acetylation status is determined by the opposing activities of lysine acetyltransferases (KATs) and lysine deacetylases (KDACs), which add and remove acetyl groups from proteins, respectively. A special group of KDACs, named sirtuins, that require NAD as a substrate have received particular attention in recent years. They play critical roles in metabolism, and their abnormal activity has been implicated in several diseases. Conversely, the modulation of their activity has been associated with protection from age-related cardiovascular and metabolic diseases and with increased longevity. The benefits of either activating or inhibiting these enzymes have turned sirtuins into attractive therapeutic targets, and considerable effort has been directed toward developing specific sirtuin modulators. This review summarizes the protein acylation/deacylation processes with a special focus on the current developments in the sirtuin research field.
蛋白质的乙酰化作用发生于氨基酸末端残基的α-氨基或内部赖氨酸或半胱氨酸残基，是细胞内发生的主要的翻译后蛋白修饰之一，对蛋白质以及代谢组水平都有影响。赖氨酸乙酰化状态由赖氨酸乙酰转移酶（KAT）和赖氨酸去乙酰化酶（KDAC）的拮抗活性决定，它们分别向蛋白质中添加和去除乙酰基。近年来，一类特殊的 KDAC，即依赖 NAD 的称为 sirtuins 的去乙酰化酶，受到了特别关注。它们在新陈代谢中发挥着关键作用，其异常活性与多种疾病有关。相反，它们的活性调节与保护与年龄相关的心血管和代谢疾病以及延长寿命有关。激活或抑制这些酶的益处使 sirtuins 成为有吸引力的治疗靶点，并且已经投入了相当大的努力来开发特定的 sirtuin 调节剂。这篇综述总结了蛋白质酰化/脱酰化过程，特别关注 sirtuins 研究领域的最新进展。
