The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; and The Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
Physiol Rev. 2020 Jan 1;100(1):145-169. doi: 10.1152/physrev.00030.2018. Epub 2019 Aug 22.
Mammalian sirtuins have emerged in recent years as critical modulators of multiple biological processes, regulating cellular metabolism, DNA repair, gene expression, and mitochondrial biology. As such, they evolved to play key roles in organismal homeostasis, and defects in these proteins have been linked to a plethora of diseases, including cancer, neurodegeneration, and aging. In this review, we describe the multiple roles of SIRT6, a chromatin deacylase with unique and important functions in maintaining cellular homeostasis. We attempt to provide a framework for such different functions, for the ability of SIRT6 to interconnect chromatin dynamics with metabolism and DNA repair, and the open questions the field will face in the future, particularly in the context of putative therapeutic opportunities.
近年来，哺乳动物的 sirtuins 作为多种生物过程的关键调节剂而出现，调节细胞代谢、DNA 修复、基因表达和线粒体生物学。因此，它们进化到在机体稳态中发挥关键作用，这些蛋白质的缺陷与多种疾病有关，包括癌症、神经退行性变和衰老。在这篇综述中，我们描述了 SIRT6 的多种作用，SIRT6 是一种具有独特而重要功能的染色质脱乙酰酶，可维持细胞稳态。我们试图为这些不同的功能提供一个框架，即 SIRT6 将染色质动力学与代谢和 DNA 修复联系起来的能力，以及该领域未来将面临的悬而未决的问题，特别是在潜在的治疗机会方面。
