UBIQUITIN AND CELL COMMUNICATION IN EYE DEVELOPMENT

眼睛发育中的泛素和细胞通讯

• 批准号: 6182120
• 负责人: JANICE A. FISCHER
• 金额: $ 24.2万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-08 至 2002-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6182120
• 关键词: Drosophilidae; cell cell interaction; developmental genetics; gene complementation; gene expression; gene mutation; genetic regulation; genetically modified animals; histogenesis; laboratory rabbit; molecular cloning; polymerase chain reaction; protein sequence; protein structure function; proteolysis; retina; ubiquitin; visual photoreceptor; yeast two hybrid system

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.

这项研究的主要目标是了解一种新的细胞 动物发育中的沟通途径。 该细胞 通讯途径以独特的方式由泛素调节， 介导的蛋白水解。 因此，该研究还提供了 关于泛素途径功能和如何作用的重要新信息 泛素调节发育。 具体的研究建议的目的是确定和了解 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， Fat Faces（脂肪小面）基因。 faf基因编码一个去泛素化的 一种调节泛素介导的蛋白水解的酶，或UBP， 特定蛋白质 在缺乏FAF蛋白的情况下，一种未知的神经细胞 抑制途径无法发挥作用，导致视网膜紊乱 含有许多异位光感受器。 基因筛选将用于识别编码 细胞通讯途径的组成部分。 分子克隆和 转基因果蝇技术将用于分离基因并研究 它们所编码的蛋白质的功能。 这些技术也将 用于进行FAF蛋白的结构/功能分析。 随着小鼠和人类faf同源物的鉴定， 由FAF调节的通信途径可能被普遍使用 在动物发展中。 泛素介导的蛋白水解调节细胞 生长和一些UBP是致癌基因。虽然泛素化可以用于 在调节蛋白质功能的磷酸化作用中， 已知泛素途径或UBPs在 多细胞生物果蝇faf突变体为我们提供了一个独特的 有机会调查一个相对未知的生化途径， 强大的基因系统