Jadhav Trafina, Wooten Marie W
Program in Cellular and Molecular Biosciences, Department of Biological Sciences, Auburn University, Auburn, AL, 36849, USA.
J Proteomics Bioinform. 2009 Jul 24;2:316. doi: 10.4172/jpb.1000091.
It has been more than 30 years since the initial report of the discovery of ubiquitin as an 8.5 kDa protein of unknown function expressed universally in living cells. And still, protein modification by covalent conjugation of the ubiquitin molecule is one of the most dynamic posttranslational modifications studied in terms of biochemistry and cell physiology. Ubiquitination plays a central regulatory role in number of eukaryotic cellular processes such as receptor endocytosis, growth-factor signaling, cell-cycle control, transcription, DNA repair, gene silencing, and stress response. Ubiquitin conjugation is a three step concerted action of the E1-E2-E3 enzymes that produces a modified protein. In this review we investigate studies undertaken to identify both ubiquitin and SUMO (small ubiquitin-related modifier) substrates with the goal of understanding how lysine selectivity is achieved. The SUMOylation pathway though distinct from that of ubiquitination, draws many parallels. Based upon the recent findings, we present a model to explain how an individual ubiquitin ligase may target specific lysine residue(s) with the co-operation from a scaffold protein.
自泛素作为一种在活细胞中普遍表达、功能未知的8.5 kDa蛋白质首次被发现的报告发表以来，已经过去了30多年。即便如此，就生物化学和细胞生理学而言，通过泛素分子的共价缀合进行蛋白质修饰仍是研究最多的动态翻译后修饰之一。泛素化在许多真核细胞过程中发挥着核心调节作用，如受体胞吞作用、生长因子信号传导、细胞周期控制、转录、DNA修复、基因沉默和应激反应。泛素缀合是E1-E2-E3酶的三步协同作用，产生一种修饰后的蛋白质。在这篇综述中，我们研究了旨在鉴定泛素和SUMO（小泛素相关修饰物）底物的研究，目的是了解赖氨酸选择性是如何实现的。SUMO化途径虽然与泛素化途径不同，但有许多相似之处。基于最近的研究发现，我们提出了一个模型来解释单个泛素连接酶如何在支架蛋白的协同作用下靶向特定的赖氨酸残基。
