Sowa Mathew E, Bennett Eric J, Gygi Steven P, Harper J Wade
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Cell. 2009 Jul 23;138(2):389-403. doi: 10.1016/j.cell.2009.04.042. Epub 2009 Jul 16.
Deubiquitinating enzymes (Dubs) function to remove covalently attached ubiquitin from proteins, thereby controlling substrate activity and/or abundance. For most Dubs, their functions, targets, and regulation are poorly understood. To systematically investigate Dub function, we initiated a global proteomic analysis of Dubs and their associated protein complexes. This was accomplished through the development of a software platform called CompPASS, which uses unbiased metrics to assign confidence measurements to interactions from parallel nonreciprocal proteomic data sets. We identified 774 candidate interacting proteins associated with 75 Dubs. Using Gene Ontology, interactome topology classification, subcellular localization, and functional studies, we link Dubs to diverse processes, including protein turnover, transcription, RNA processing, DNA damage, and endoplasmic reticulum-associated degradation. This work provides the first glimpse into the Dub interaction landscape, places previously unstudied Dubs within putative biological pathways, and identifies previously unknown interactions and protein complexes involved in this increasingly important arm of the ubiquitin-proteasome pathway.
去泛素化酶（Dubs）的功能是从蛋白质上去除共价连接的泛素，从而控制底物活性和/或丰度。对于大多数去泛素化酶而言，它们的功能、靶点和调控机制尚不清楚。为了系统地研究去泛素化酶的功能，我们启动了一项对去泛素化酶及其相关蛋白复合物的全蛋白质组分析。这是通过开发一个名为CompPASS的软件平台来实现的，该平台使用无偏倚的指标为来自平行非互作蛋白质组数据集的相互作用分配置信度测量值。我们鉴定出了与75种去泛素化酶相关的774种候选相互作用蛋白。通过基因本体论、相互作用组拓扑结构分类、亚细胞定位和功能研究，我们将去泛素化酶与多种过程联系起来，包括蛋白质周转、转录、RNA加工、DNA损伤和内质网相关降解。这项工作首次揭示了去泛素化酶的相互作用图谱，将以前未研究的去泛素化酶置于假定的生物学途径中，并鉴定出了参与泛素-蛋白酶体途径这一日益重要分支的先前未知的相互作用和蛋白复合物。
