Gregori L, Bhasin R, Goldgaber D
Department of Psychiatry and Behavioral Science, State University of New York at Stony Brook.
Biochem Biophys Res Commun. 1994 Sep 30;203(3):1731-8. doi: 10.1006/bbrc.1994.2386.
The presence of ubiquitin and ubiquitin conjugates has been detected in patients affected by neurodegenerative diseases such as Alzheimer's disease. We investigated the role of ubiquitin in the degradation of amyloid beta-protein precursor (APP) and its participation in the process of amyloid beta-protein formation. APP was tested as a substrate for ubiquitin-mediated degradation, using both the extracellular and the intracellular forms of APP770, APP751 and APP695. The intracellular APP forms did not show appreciable ubiquitin-mediated degradation. In contrast, the three extracellular forms of APP were degraded in vitro by this proteolytic pathway, with similar degradation rates. Our results suggest a potential regulatory role for the ubiquitin-dependent degradation mechanism in the in vivo APP metabolic pathway.
在患有诸如阿尔茨海默病等神经退行性疾病的患者中已检测到泛素和泛素缀合物的存在。我们研究了泛素在淀粉样β蛋白前体（APP）降解中的作用及其在淀粉样β蛋白形成过程中的参与情况。使用APP770、APP751和APP695的细胞外和细胞内形式，将APP作为泛素介导降解的底物进行测试。细胞内APP形式未显示出明显的泛素介导降解。相反，APP的三种细胞外形式在体外通过这种蛋白水解途径被降解，降解速率相似。我们的结果表明泛素依赖性降解机制在体内APP代谢途径中具有潜在的调节作用。
