a Department of Cardiac Development and Remodeling , Max-Planck-Institute for Heart and Lung Research , Bad Nauheim , Germany.
b The State Key Laboratory of Medicinal Chemical Biology, School of Medicine , Nankai University , Tianjin , China.
Cell Cycle. 2018;17(12):1403-1412. doi: 10.1080/15384101.2018.1486166. Epub 2018 Jul 25.
Sirtuins regulate a variety of cellular processes through protein deacetylation. The best-known member of mammalian sirtuin family, Sirt1, plays important roles in the maintenance of cellular homeostasis by regulating cell metabolism, differentiation and stress responses, among others. Sirt1 activity requires tight regulation to meet specific cellular requirements, which is achieved at different levels and by specific mechanisms. Recently, a regulatory loop between Sirt1 and another sirtuin, Sirt7, was identified. Sirt7 inhibits Sirt1 autodeacetylation at K230 and activation thereby preventing Sirt1-mediated repression of adipocyte differentiation by inhibition of the PPARγ gene. Here, we extend the regulatory complexity of Sirt7-dependent restriction of Sirt1 activity by demonstrating that Sirt7 reduces activation of a previously described prominent Sirt1 target, the histone methyltransferase Suv39h1. We show that removal of the acetyl-group at K230 in Sirt1 due to the absence of Sirt7 leads to hyperactivation of Sirt1 and thereby to constantly increased activity of Suv39h1.
Sirtuins 通过蛋白去乙酰化作用调节多种细胞过程。哺乳动物 Sirtuin 家族中最为人熟知的成员 Sirt1 通过调节细胞代谢、分化和应激反应等，在维持细胞内稳态方面发挥着重要作用。Sirt1 的活性需要严格的调控以满足特定的细胞需求，这是通过不同的水平和特定的机制来实现的。最近，发现了 Sirt1 和另一个 Sirtuin（Sirt7）之间的一个调节环。Sirt7 通过抑制 Sirt1 的 K230 自去乙酰化和激活，从而阻止 Sirt1 对脂肪细胞分化的抑制作用，抑制 PPARγ 基因。在这里，我们通过证明 Sirt7 降低了先前描述的 Sirt1 主要靶标之一组蛋白甲基转移酶 Suv39h1 的活性，扩展了 Sirt7 依赖性限制 Sirt1 活性的调节复杂性。我们表明，由于 Sirt7 的缺失，Sirt1 中 K230 上的乙酰基被去除，导致 Sirt1 过度激活，从而导致 Suv39h1 的活性不断增加。
