Toiber Debra, Sebastian Carlos, Mostoslavsky Raul
The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Handb Exp Pharmacol. 2011;206:189-224. doi: 10.1007/978-3-642-21631-2_9.
Sirtuins are protein deacetylases/mono-ADP-ribosyltransferases found in organisms ranging from bacteria to humans. This group of enzymes relies on nicotinamide adenine dinucleotide (NAD(+)) as a cofactor linking their activity to the cellular metabolic status. Originally found in yeast, Sir2 was discovered as a silencing factor and has been shown to mediate the effects of calorie restriction on lifespan extension. In mammals seven homologs (SIRT1-7) exist which evolved to have specific biological outcomes depending on the particular cellular context, their interacting proteins, and the genomic loci to where they are actively targeted. Sirtuins biological roles are highlighted in the early lethal phenotypes observed in the deficient murine models. In this chapter, we summarize current concepts on non-metabolic functions for sirtuins, depicting this broad family from yeast to mammals.
沉默调节蛋白是一类蛋白质脱乙酰酶/单ADP核糖基转移酶，存在于从细菌到人类的各种生物体中。这类酶依赖烟酰胺腺嘌呤二核苷酸（NAD(+)）作为辅助因子，将其活性与细胞代谢状态联系起来。Sir2最初是在酵母中发现的，被作为一种沉默因子，并且已被证明可介导热量限制对寿命延长的影响。在哺乳动物中存在七个同源物（SIRT1 - 7），它们根据特定的细胞环境、相互作用的蛋白质以及它们被主动靶向的基因组位点而进化出特定的生物学结果。在缺乏沉默调节蛋白的小鼠模型中观察到的早期致死表型突出了沉默调节蛋白的生物学作用。在本章中，我们总结了关于沉默调节蛋白非代谢功能的当前概念，描绘了从酵母到哺乳动物的这个广泛的家族。
