Macias Maria J, Martin-Malpartida Pau, Massagué Joan
Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10, 08028 Barcelona, Spain; Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluis Companys 23, 08010 Barcelona, Spain.
Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10, 08028 Barcelona, Spain.
Trends Biochem Sci. 2015 Jun;40(6):296-308. doi: 10.1016/j.tibs.2015.03.012. Epub 2015 Apr 29.
Smad transcription factors are central to the signal transduction pathway that mediates the numerous effects of the transforming growth factor β (TGF-β) superfamily of cytokines in metazoan embryo development as well as in adult tissue regeneration and homeostasis. Although Smad proteins are conserved, recent genome-sequencing projects have revealed their sequence variation in metazoan evolution, human polymorphisms, and cancer. Structural studies of Smads bound to partner proteins and target DNA provide a framework for understanding the significance of these evolutionary and pathologic sequence variations. We synthesize the extant mutational and structural data to suggest how genetic variation in Smads may affect the structure, regulation, and function of these proteins. We also present a web application that compares Smad sequences and displays Smad protein structures and their disease-associated variants.
Smad转录因子是信号转导途径的核心，该途径介导了后生动物胚胎发育、成体组织再生和体内平衡过程中细胞因子转化生长因子β（TGF-β）超家族的多种效应。尽管Smad蛋白具有保守性，但最近的基因组测序项目揭示了它们在后生动物进化、人类多态性和癌症中的序列变异。对与伴侣蛋白和靶DNA结合的Smad蛋白进行的结构研究为理解这些进化和病理序列变异的意义提供了一个框架。我们综合现有的突变和结构数据，以表明Smad基因变异如何影响这些蛋白的结构、调控和功能。我们还展示了一个网络应用程序，该程序可比较Smad序列，并展示Smad蛋白结构及其与疾病相关的变体。
