Département de médecine, Université de Montréal, Montréal, QC, Canada; Axe cardio-métabolique, Centre de Recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, Québec, Canada.
Département de médecine, Université de Montréal, Montréal, QC, Canada; Axe cardio-métabolique, Centre de Recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, Québec, Canada.
Pharmacol Res. 2019 Jan;139:199-206. doi: 10.1016/j.phrs.2018.11.021. Epub 2018 Nov 16.
Since their initial characterization as abundant brain proteins more than 5 decades ago, a resurgence into understanding the cellular functions of 14-3-3 proteins has emerged. While one of the earliest functions attributed to this eukaryotic scaffold protein family was the activation of enzymes involved in catecholamine and serotonin biosynthesis, 14-3-3 proteins have since been implicated in the regulation of several cellular processes including cell-cycle control, apoptosis, and metabolism. Moreover, increasing lines of evidence demonstrate links between changes in 14-3-3 protein function and the pathogenesis of chronic diseases. As a result, this has raised the question of whether 14-3-3 proteins represent viable targets for pharmacological intervention against diseases such as obesity, diabetes and cancer. In addition to providing an overview of the 14-3-3 protein family, we will discuss their connections to metabolism and metabolic diseases. We will also elaborate on the potential of targeting 14-3-3 proteins, as well as components of their interactomes, for developing novel therapies for treating metabolic diseases, including diabetes and obesity.
自 50 多年前首次被描述为丰富的大脑蛋白质以来，人们对了解 14-3-3 蛋白的细胞功能重新产生了兴趣。虽然该真核支架蛋白家族的最早功能之一是激活儿茶酚胺和 5-羟色胺生物合成中涉及的酶，但此后，14-3-3 蛋白已被牵连到包括细胞周期控制、细胞凋亡和代谢在内的多种细胞过程的调节中。此外，越来越多的证据表明，14-3-3 蛋白功能的变化与慢性疾病的发病机制之间存在联系。因此，人们提出了这样一个问题，即 14-3-3 蛋白是否可以作为肥胖症、糖尿病和癌症等疾病的药理学干预的可行靶点。除了概述 14-3-3 蛋白家族外，我们还将讨论它们与代谢和代谢性疾病的关系。我们还将详细阐述针对 14-3-3 蛋白及其相互作用组的成分来开发治疗代谢性疾病（包括糖尿病和肥胖症）的新型疗法的潜力。
