Identification and characterization of target proteins of the ubiquitin-protein ligase E6-AP (Identifizierung von Zielproteinen der putativen Ubiquitin-Proteinligase E6-AP)

泛素蛋白连接酶 E6-AP 靶蛋白的鉴定和表征

• 批准号: 5109924
• 负责人: Professor Dr. Martin Scheffner
• 金额: --
• 依托单位: Arbeitsgruppe Zelluläre Biochemie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 1998
• 资助国家: 德国
• 起止时间: 1997-12-31 至 2004-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5109924?language=en
• 关键词: Identification; characterization; target; proteins; ubiquitin

The recognition of substrate proteins by the ubiquitin-conjugation system is a specific and, at least in some instances, regulated event. It is widely assumed that ubiquitin-conjugating enzymes and, in particular, ubiquitin-protein ligases play a major role in mediating substrate recognition. Over the past few years, several proteins or protein families with ubiquitinprotein ligase activity have been identified including the SCF family and the hect domain family. Members of the hect domain family are found in all eukaryotic organisms so far examined and the human genome encodes at least 20 different hect domain proteins. However, the physiologic function and the substrates of most hect domain proteins are unknown at present. The principal aim of this proposal is the identification and characterization of target proteins of two human hect domain proteins, E6-AP and hsORFK/HectH3. Interestingly, loss of function of the E6-AP gene results in a neurodegenerative disorder, the Angelman Syndrome. Thus, these studies should contribute to the elucidation of the physiologic role of these proteins in general and of the role of disregulated protein degradation in the development of the Angelman Syndrome in particular.

泛素结合系统对底物蛋白的识别是一种特异性的，至少在某些情况下是受调控的事件。普遍认为泛素结合酶，特别是泛素-蛋白质连接酶在介导底物识别中起主要作用。在过去的几年中，已经鉴定了几种具有泛素蛋白连接酶活性的蛋白质或蛋白质家族，包括SCF家族和hect结构域家族。hect结构域家族成员存在于所有的真核生物中，人类基因组编码至少20种不同的hect结构域蛋白。然而，目前大多数hect结构域蛋白的生理功能和底物尚不清楚。本发明的主要目的是鉴定和表征两种人hect结构域蛋白E6-AP和hsORFK/HectH 3的靶蛋白。有趣的是，E6-AP基因功能的丧失导致神经退行性疾病，即Angelman综合征。因此，这些研究应有助于阐明这些蛋白质的生理作用，特别是Angelman综合征的发展中失调的蛋白质降解的作用。