Functional characterisation of N4WBP5 and N4WBP5A, novel Nedd4-interacting proteins

组成细胞的蛋白质必须正确定位，以执行其正常功能。专门的细胞活动在细胞内的不同隔室中进行，蛋白质必须正确地定位在它们中并在它们之间进行运输。细胞内蛋白质运输是一个高度调控的过程，涉及许多组件。最近的研究结果表明，在许多情况下，细胞内运输是由不同的蛋白质修饰。其中一种修饰是将一种叫做泛素的小蛋白质标记到被贩运的蛋白质上。我们实验室的研究重点是研究一种名为Nedd4的蛋白质，它直接用泛素标记蛋白质。我们最近发现了两种新的蛋白质，它们与Nedd4相互作用，并定位于不同的亚细胞区室，这些亚细胞区室是细胞内蛋白质运输的正确分选和递送位点。我们计划的主要目的是研究这些蛋白质的功能。我们认为这些蛋白质参与细胞内运输，它们可能通过将Nedd4靶向细胞运输机制发挥作用。这可能需要Nedd4用参与细胞内运输的泛素标记分子。我们的实验将测试Nedd4和新蛋白质之间的功能关系，并确定这些蛋白质参与的特定运输途径。由Nedd4和其他类似蛋白质调节的细胞过程的缺陷会导致许多人类疾病，包括遗传性高血压和特定的癌症。此外，许多人类疾病直接由破坏细胞内运输途径的缺陷引起。这项研究的结果将进一步深入了解这一重要的细胞过程，并可能最终有助于开发治疗细胞内运输缺陷引起的疾病的疗法。

The proteins that make up a cell must be correctly localised in order to perform their normal function. Specialised cellular activities are carried out in distinct compartments within a cell and proteins must correctly localise in them and traffic between them. Intracellular protein trafficking is a highly regulated process involving many components. Recent findings have shown that intracellular trafficking is regulated in many cases by distinct protein modifications. One such modification is tagging of a small protein called ubiquitin to proteins that are being trafficked. A focus of research in our laboratory is the study of a protein, called Nedd4, which directly tags proteins with ubiquitin. We have recently identified two novel proteins that interact with Nedd4 and localise to distinct subcellular compartments that are sites for the correct sorting and delivery of proteins trafficking within the cell. The main aim of our proposal is to characterise how these proteins function. We propose that these proteins are involved in intracellular trafficking and that they may function by targeting Nedd4 to the cellular trafficking machinery. This may be required for Nedd4 to tag molecules with ubiquitin that are involved in intracellular trafficking. Our experiments will test the functional relationship between Nedd4 and the novel proteins and determine the particular trafficking pathways in which these proteins are involved. Defects in cellular processes regulated by Nedd4 and other similar proteins cause a number of human diseases including an inherited form of hypertension and a specific group of cancers. In addition, a large number of human diseases result directly from defects which disrupt intracellular trafficking pathways. The results of this study will provide further insight into this essential cellular process and may ultimately contribute to the development of therapies for diseases resulting from defects in intracellular trafficking.