PROTEIN DEGRADATION DURING VERTEBRATE EMBRYOGENESIS

脊椎动物胚胎发生过程中的蛋白质降解

• 批准号: 6752540
• 负责人: ZHENGLUN ZHU
• 金额: $ 13.39万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6752540
• 关键词: DNA binding protein; Xenopus; developmental genetics; gene expression; homeobox genes; nonmammalian vertebrate embryology; protein degradation; ubiquitin

Regulated protein degradation by the unbiquitin medicated pathway is emerges as an important mechanism for regulating gene function. Although implicated in few pathways of developmental control, little is known about the extent of the role of regulated protein degradation during embryogenesis. Since broadly speaking, mis-regulation of specific genes involved in development has been implicated in several malignancies, it is likely that protein degradation will have increasing clinical significance. To explore the function of regulate protein degradation during development, we employed a novel method of screening small pools of Xenopus cDNAs to identify genes that are degraded at different stages of embryonic development. In my initial search, I found that Xom., a Xenopus homeobox gene, is degraded in a stage specific manner, most likely through the unbiquitin pathway. Previous studies suggested that Xom. plays am important role in dorsal-ventral pattern formation. Therefore, we hypothesized that the stage specific degradation of Xom. could be important for proper expression of Xom. during embryogenesis. In the future experiments, we will try to identify the mechanism of Xom degradation and study any developmental defects caused by expression of non-degradable mutants of Xor. during embryogenesis. We will also continue to screen genes that are degraded in stage specific manner and determine whether they play important role during development.

通过泛素介导途径调节蛋白质降解是调节基因功能的重要机制。虽然涉及几个途径的发育控制，很少有人知道的程度，在胚胎发生过程中的调节蛋白质降解的作用。由于广义上讲，参与发育的特定基因的错误调节与几种恶性肿瘤有关，因此蛋白质降解可能具有越来越大的临床意义。为了探索在发育过程中调节蛋白质降解的功能，我们采用了一种新的方法，筛选非洲爪蟾cDNA的小池，以确定在胚胎发育的不同阶段降解的基因。在我最初的搜索中，我发现Xom.，非洲爪蟾同源框基因，以阶段特异性方式降解，最有可能是通过unbiquitin途径。以前的研究表明，Xom。在背腹纹的形成中起重要作用。因此，我们假设Xom的阶段特异性降解。对于Xom的正确表达可能很重要。在胚胎发生期间。在未来的实验中，我们将尝试确定Xom降解的机制，并研究Xor的非降解突变体的表达所引起的任何发育缺陷。在胚胎发育过程中。我们还将继续筛选以阶段特异性方式降解的基因，并确定它们是否在发育过程中发挥重要作用。