STRUCTURAL AND FUNCTIONAL STUDIES OF DJ-1

DJ-1 的结构和功能研究

• 批准号: 7381841
• 负责人: MARK A WILSON
• 金额: $ 17.33万
• 依托单位: UNIVERSITY OF NEBRASKA LINCOLN
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381841
• 关键词: STRUCTURAL; FUNCTIONAL; STUDIES; DJ

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The human protein DJ-1 has been implicated both in hereditary Parkinsonism and in certain cancers and appears to play a critical role in protecting cells from the damaging effects of oxidative stress. Oxidative stress has been linked to the molecular pathogenesis of several diseases, and may play a key role in the etiology of Parkinson's disease. The biochemical mechanism by which DJ-1 protects cells is unknown, however it is specifically modified by reactive oxygen species (ROS) by formation of cysteine sulfinic acid. This oxidation of DJ-1 activates a chaperone function that suppresses the cytotoxic aggregation of alpha-synuclein, alters the protein binding partners for DJ-1, and may increase the pool of DJ-1 that is localized to the mitochondria.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。人类蛋白质 DJ-1 与遗传性帕金森症和某些癌症有关，并且似乎在保护细胞免受氧化应激的破坏性影响方面发挥着关键作用。氧化应激与多种疾病的分子发病机制有关，并且可能在帕金森病的病因学中发挥关键作用。 DJ-1 保护细胞的生化机制尚不清楚，但它可通过形成半胱氨酸亚磺酸而被活性氧 (ROS) 特异性修饰。 DJ-1 的这种氧化会激活伴侣功能，抑制 α-突触核蛋白的细胞毒性聚集，改变 DJ-1 的蛋白质结合伴侣，并可能增加定位于线粒体的 DJ-1 库。