Physiological and Pathogenic Roles of Prolyl Isomerase Pin1 in Metabolic Regulations via Multiple Signal Transduction Pathway Modulations.
Physiological and Pathogenic Roles of Prolyl Isomerase Pin1 in Metabolic Regulations via Multiple Signal Transduction Pathway Modulations.
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DOI：
10.3390/ijms17091495
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发表时间：
2016-09-07
影响因子：
5.6
通讯作者：
Asano T
中科院分区：
文献类型：
--
作者：
Nakatsu Y;Matsunaga Y;Yamamotoya T;Ueda K;Inoue Y;Mori K;Sakoda H;Fujishiro M;Ono H;Kushiyama A;Asano T
Prolyl异构酶分为三类，FKBP家族、亲环素和小球蛋白家族(Pin1和Par14)。在这些异构酶中，Pin1是一种与包括pSer/pThr-Pro在内的基序结合的独特的Pro基异构酶，它被激酶磷酸化。一旦结合，Pin1通过改变Pro的顺式和转换式来调节酶的活性、蛋白质的稳定性或靶蛋白质的亚细胞定位。几项研究已经研究了Pin1在癌症和阿尔茨海默病发病机制中的作用。另一方面，最近的研究表明Pin1参与调节糖脂代谢。有趣的是，虽然高脂饮食显著增加了Pin1的表达，但Pin1 KO小鼠对饮食诱导的肥胖、非酒精性脂肪性肝炎和糖尿病血管功能障碍具有抵抗力。这些现象是由于PIN1与几个调节代谢功能的关键因子结合所致，这些关键因子包括胰岛素受体底物-1、AMPK、CRTC2和NF-κB p65。本文从信号转导与代谢功能之间关系的角度，着重阐述了Pin1的生理功能以及与该异构酶相关的疾病的发病机制。
Prolyl isomerases are divided into three groups, the FKBP family, Cyclophilin and the Parvulin family (Pin1 and Par14). Among these isomerases, Pin1 is a unique prolyl isomerase binding to the motif including pSer/pThr-Pro that is phosphorylated by kinases. Once bound, Pin1 modulates the enzymatic activity, protein stability or subcellular localization of target proteins by changing the cis- and trans-formations of proline. Several studies have examined the roles of Pin1 in the pathogenesis of cancers and Alzheimer’s disease. On the other hand, recent studies have newly demonstrated Pin1 to be involved in regulating glucose and lipid metabolism. Interestingly, while Pin1 expression is markedly increased by high-fat diet feeding, Pin1 KO mice are resistant to diet-induced obesity, non-alcoholic steatohepatitis and diabetic vascular dysfunction. These phenomena result from the binding of Pin1 to several key factors regulating metabolic functions, which include insulin receptor substrate-1, AMPK, Crtc2 and NF-κB p65. In this review, we focus on recent advances in elucidating the physiological roles of Pin1 as well as the pathogenesis of disorders involving this isomerase, from the viewpoint of the relationships between signal transductions and metabolic functions.
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影响因子：
29
作者：
Gowans GJ;Hawley SA;Ross FA;Hardie DG
通讯作者：
Hardie DG
影响因子：
64.8
作者：
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通讯作者：
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影响因子：
10.5
作者：
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影响因子：
20.3
作者：
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通讯作者：
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影响因子：
3.5
作者：
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通讯作者：
Hardie, DG