UBIQUITIN AND CELL COMMUNICATION IN EYE DEVELOPMENT

这项拟议研究的主要目标是了解一种新的细胞 动物发育中使用的交流途径。这间牢房 通讯途径由泛素以一种独特的方式调节- 介导的蛋白质分解。因此，拟议的研究还提供了 关于泛素途径功能及其如何发挥作用的重要新信息 泛素调节发育。 建议的具体研究旨在识别和了解 构成新细胞的蛋白质之间的相互作用 果蝇眼睛发育过程中使用的通讯途径 脂肪面(Faf)基因。Faf基因编码一种去泛素化 调节泛素介导的蛋白分解的酶，或UBP 特定的蛋白质。在缺乏Faf蛋白的情况下，一种未知的神经 抑制通路失灵，导致视网膜组织紊乱 含有许多异位的光感受器。 基因筛查将被用来识别编码 细胞通讯途径的组成部分。分子克隆和 转基因苍蝇技术将用于分离这些基因并进行研究 它们所编码的蛋白质的功能。这些技术还将 用于进行Faf蛋白的结构/功能分析。 随着鼠和人的Faf同源物被鉴定出来，细胞 FAF调控的通讯通路有可能被普遍使用 在动物发育方面。泛素介导的蛋白降解对细胞的调节 生长和一些UBP是癌基因。尽管可以使用泛素化 在调节蛋白质功能方面与磷酸化一样广泛，但很少 已知泛素途径或UBP在 多细胞生物。果蝇Faf突变体为我们提供了一种独特的 有机会研究一种相对未知的生化途径 一个强大的基因系统。

The broad goal of the proposed research is to understand a novel cell communication pathway used in animal development. This cell communication pathway is regulated in a unique manner by ubiquitin- mediated proteolysis. Thus, the proposed research also provide important new information about ubiquitin pathway function and about how ubiquitin regulates development. The specific research proposed aims to identify and understand the interactions of the proteins that constitute the novel cell communication pathway used during Drosophila eye development defined by the fat facets (faf) gene. The faf gene encodes a deubiquitinating enzyme, or UBP, that regulates the ubiquitin-mediated proteolysis of specific proteins. In the absence of FAF protein, an unknown neural inhibition pathway fails to function, resulting in disorganized retinas containing many ectopic photoreceptors. Genetic screens will be used to identify the genes encoding the components of the cell communication pathway. Molecular cloning and transgenic fly technology will be used to isolate the genes and study the functions of the proteins they encode. These techniques will also be used to perform a structure/function analysis of the FAF protein. As mouse and human faf homologs have been identified, the cell communication pathway regulated by faf is likely to be used universally in animal development. Ubiquitin-mediated proteolysis regulates cell growth and some UBPs are oncogenes. Although ubiquitination may be used as widely as phosphorylation in regulating protein function, very little is known about the role of the ubiquitin pathway or UBPs in multicellular organisms. Drosophila faf mutants provide us with a unique opportunity to investigate a relatively unknown biochemical pathway in a powerful genetic system.