PROTEIN DEGRADATION DURING VERTEBRATE EMBRYOGENESIS

脊椎动物胚胎发生过程中的蛋白质降解

基本信息

批准号：
6904637
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
项目类别：
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/6904637
关键词：
DNA binding protein Xenopus developmental genetics gene expression homeobox genes nonmammalian vertebrate embryology protein degradation ubiquitin

项目摘要

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.

通过单泛素药物途径调节蛋白质降解已成为调节基因功能的重要机制。尽管涉及发育控制的途径很少，但人们对胚胎发生过程中受调节的蛋白质降解的作用程度知之甚少。从广义上讲，参与发育的特定基因的错误调节与多种恶性肿瘤有关，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爪蟾 cDNA 的小池，以鉴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）以特定阶段的方式降解，最有可能通过非泛素途径降解。先前的研究表明 Xom。在背腹模式的形成中起着重要作用。因此，我们假设 Xom 存在阶段特异性降解。对于 Xom 的正确表达可能很重要。在胚胎发生过程中。在未来的实验中，我们将尝试确定Xom降解的机制，并研究由不可降解的Xor突变体表达引起的发育缺陷。在胚胎发生过程中。我们还将继续筛选以阶段特异性方式降解的基因，并确定它们在发育过程中是否发挥重要作用。