Saunders L R, Verdin E
Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA, USA.
Oncogene. 2007 Aug 13;26(37):5489-504. doi: 10.1038/sj.onc.1210616.
Sirtuins (SIRTs 1-7), or class III histone deacetylases (HDACs), are protein deacetylases/ADP ribosyltransferases that target a wide range of cellular proteins in the nucleus, cytoplasm, and mitochondria for post-translational modification by acetylation (SIRT1, -2, -3 and -5) or ADP ribosylation (SIRT4 and -6). The orthologs of sirtuins in lower organisms play a critical role in regulating lifespan. As cancer is a disease of aging, we discuss the growing implications of the sirtuins in protecting against cancer development. Sirtuins regulate the cellular responses to stress and ensure that damaged DNA is not propagated and that mutations do not accumulate. SIRT1 also promotes replicative senescence under conditions of chronic stress. By participating in the stress response to genomic insults, sirtuins are thought to protect against cancer, but they are also emerging as direct participants in the growth of some cancers. Here, we review the growing implications of sirtuins both in cancer prevention and as specific and novel cancer therapeutic targets.
沉默调节蛋白（SIRT1 - 7），即Ⅲ类组蛋白去乙酰化酶（HDACs），是蛋白质去乙酰化酶/ADP核糖基转移酶，可作用于细胞核、细胞质和线粒体中的多种细胞蛋白，通过乙酰化（SIRT1、-2、-3和-5）或ADP核糖基化（SIRT4和-6）进行翻译后修饰。低等生物中的沉默调节蛋白直系同源物在调节寿命方面起着关键作用。由于癌症是一种衰老相关疾病，我们讨论了沉默调节蛋白在预防癌症发生方面日益增加的影响。沉默调节蛋白调节细胞对压力的反应，并确保受损DNA不会传播且突变不会积累。SIRT1还在慢性应激条件下促进复制性衰老。通过参与对基因组损伤的应激反应，沉默调节蛋白被认为具有抗癌作用，但它们也逐渐成为某些癌症生长的直接参与者。在此，我们综述了沉默调节蛋白在癌症预防以及作为特定和新型癌症治疗靶点方面日益增加的影响。
