Sirtuins在与各种代谢调节相关的信号通路中起重要作用。它们具有单ADP-核糖基转移酶或脱酰酶活性,如脱甲醛酶,脱乙酰酶,脱棕榈酶,脱胞嘧啶酶和脱琥珀酶活性。Sirtuins是组蛋白脱乙酰酶,其依赖于使赖氨酸残基脱乙酰的烟酰胺腺嘌呤二核苷酸(NAD)。总共有七种人类沉默调节蛋白被鉴定出来,SIRT1、SIRT2、SIRT3、SIRT4、SIRT5、SIRT6和SIRT7。哺乳动物沉默调节蛋白的亚细胞位置,SIRT1,SIRT6和SIRT7在细胞核中;SIRT3,SIRT4和SIRT5在线粒体中,SIRT2在细胞质中。结构上的sirtuins包含一个N端,C-末端和Zn+结合结构域。已发现sirtuin家族对于维持脂质和葡萄糖稳态至关重要,以及调节胰岛素分泌和敏感性,DNA修复途径,神经发生,炎症,和衰老。根据文献,沉默调节蛋白在非小细胞肺癌等各种类型的癌症中过度表达并在致瘤性中起重要作用,结直肠癌,等。在这次审查中,我们已经讨论了不同类型的人类沉默调节蛋白及其结构和功能特征。我们还讨论了sirtuin活性的各种天然和合成调节剂,如白藜芦醇。我们的总体研究表明,沉默调节蛋白的正确调节可以成为预防和治疗各种疾病以改善人类寿命的良好目标。探讨沉默酶蛋白的真正治疗潜力及其在多种病理疾病中的疗效,更好地了解sirtuin蛋白的结构和功能之间的联系是必要的。
Sirtuins play an important role in signalling pathways associated with various metabolic regulations. They possess mono-ADP-ribosyltransferase or deacylase activity like demalonylase,
deacetylase, depalmitoylase, demyristoylase and desuccinylase activity. Sirtuins are histone deacetylases which depends upon nicotinamide adenine dinucleotide (NAD) that deacetylate lysine residues. There are a total of seven human sirtuins that have been identified namely, SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6 and SIRT7. The subcellular location of mammalian sirtuins, SIRT1, SIRT6, and SIRT7 are in the nucleus; SIRT3, SIRT4, and SIRT5 are in mitochondria, and SIRT2 is in cytoplasm. Structurally sirtuins contains a N-terminal, a C-terminal and a Zn+ binding domain. The sirtuin family has been found to be crucial for maintaining lipid and glucose homeostasis, and also for regulating insulin secretion and sensitivity, DNA repair pathways, neurogenesis, inflammation, and ageing. Based on the literature, sirtuins are overexpressed and play an important role in tumorigenicity in various types of cancer such as non-small cell lung cancer, colorectal cancer, etc. In this
review, we have discussed about the different types of human sirtuins along with their structural and functional features. We have also discussed about the various natural and synthetic regulators of sirtuin activities like resveratrol. Our overall study shows that the correct regulation of sirtuins can be a good target for preventing and treating various diseases for improving the human lifespan. To investigate the true therapeutic potential of sirtuin proteins and their efficacy in a variety of pathological diseases, a better knowledge of the link between the structure and function of sirtuin proteins would be necessary.