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: 6516801
• 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/6516801
• 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.

由Unbiquitin调控的蛋白质降解途径是调节基因功能的重要机制。虽然与少数发育控制途径有关，但人们对胚胎发育过程中蛋白质降解的调控程度知之甚少。由于广泛地说，与发育相关的特定基因的错误调控已与几种恶性肿瘤有关，因此蛋白质降解可能具有越来越重要的临床意义。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来筛选非洲爪哇cDNA小池，以识别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.，一个非洲爪哇的同源盒基因，以一种特定阶段的方式降解，很可能是通过Unbiquitin途径。以前的研究表明，XOM。在背腹模式的形成中起着重要作用。因此，我们假设XOM的降解是阶段性的。可能对XOM的正确表达很重要。在胚胎发育过程中。在未来的实验中，我们将试图确定XOM的降解机制，并研究XOR非降解突变体的表达是否会导致发育缺陷。在胚胎发育过程中。我们还将继续筛选以特定阶段方式降解的基因，并确定它们是否在发育过程中发挥重要作用。