Sauve Anthony A, Wolberger Cynthia, Schramm Vern L, Boeke Jef D
Department of Pharmacology, Weill Medical College of Cornell University, New York, New York 10021, USA.
Annu Rev Biochem. 2006;75:435-65. doi: 10.1146/annurev.biochem.74.082803.133500.
Sirtuins are a family of NAD+-dependent protein deacetylases widely distributed in all phyla of life. Accumulating evidence indicates that sirtuins are important regulators of organism life span. In yeast, these unique enzymes regulate gene silencing by histone deacetylation and via formation of the novel compound 2'-O-acetyl-ADP-ribose. In multicellular organisms, sirtuins deacetylate histones and transcription factors that regulate stress, metabolism, and survival pathways. The chemical mechanism of sirtuins provides novel opportunities for signaling and metabolic regulation of protein deacetylation. The biological, chemical, and structural characteristics of these unusual enzymes are discussed in this review.
沉默调节蛋白是一类依赖烟酰胺腺嘌呤二核苷酸（NAD+）的蛋白质脱乙酰酶，广泛分布于所有生物门类中。越来越多的证据表明，沉默调节蛋白是生物体寿命的重要调节因子。在酵母中，这些独特的酶通过组蛋白去乙酰化以及通过形成新型化合物2'-O-乙酰基-ADP-核糖来调节基因沉默。在多细胞生物中，沉默调节蛋白使组蛋白和转录因子脱乙酰化，这些组蛋白和转录因子调节应激、代谢和生存途径。沉默调节蛋白的化学机制为蛋白质脱乙酰化的信号传导和代谢调节提供了新的机会。本文综述讨论了这些特殊酶的生物学、化学和结构特征。
