Sirtuin 4和Sirtuin 5蛋白在代谢性疾病与肿瘤中的研究进展

Progress in the research of Sirtuin 4/5 proteins in metabolic diseases and tumors:A review

沉默调节蛋白(Sirtuin,Sirt)是一类具有多种代谢调节酶活性的蛋白质家族,Sirtuin家族成员共有7个(Sirt 1～7),其成员中Sirt 4蛋白具有NAD依赖的蛋白脂酰胺酶、ADP-核糖体转移酶和赖氨酸去酰基酶的活性,而Sirt 5蛋白具有NAD-依赖的赖氨酸去丙二酰酶、去琥珀酰酶和去戊二酰酶的活性。近年来研究发现,Sirt 4和Sirt 5广泛参与到细胞生存、衰老和代谢等生物学过程中,在生物体应激反应、炎症反应、肿瘤发生和能量代谢等众多生物学过程中扮演着重要角色,并在癌症、糖尿病、肥胖、帕金森和阿尔兹海默病等疾病的临床治疗方面具有一定潜力。本文归纳了Sirt 4和Sirt 5在代谢途径中的重要作用,并归纳了其与代谢性疾病及癌症的关系,希望能够为开发相关癌症的靶向药物、临床治疗提供新思路。

Sirtuins （Sirts） are a family of proteins with multiple enzymatic activities responsible for metabolism regulation,consists of 7 members （Sirt 1-7）.Among which,the Sirt 4 possesses NAD-dependent protein lipoamidase,ADP-ribosomal transferase and lysine deacylase activity,whereas Sirt 5 possesses NAD-dependent lysine demalonylase,desuccinylase and deglutarylase activity.Recent studies have found that Sirt4 and Sirt 5 participate in a wide range of cellular processes including cell survival,aging and metabolisms,as well as multiple biological processes like stress reaction,inflammation,tumorigenesis and energy metabolism.Futhermore,Sirt 4 and Sirt 5 are potential targets that can be utilized in the treatment of cancer,diabetes mellitus,obesity,Parkinson＇s disease and Alzheimer＇s disease.In this review,we investigated and concluded the crucial actions of Sirt 4 and Sirt 5 on metabolic pathways and their relations to metabolic diseases and cancers,by which we wish to provide insights to the development of more targeted therapies against these diseases.